Apparatus and method for endovascular device guiding and positioning using physiological parameters

ABSTRACT

An endovascular navigation system and method are disclosed. The endovascular navigation system includes an elongate flexible member configured to access the venous vasculature of a patient, a processor, and a display. The elongate flexible member includes an endovascular electrogram lead disposed at a distal end of the elongate flexible member and configured to sense an endovascular electrogram signal of the venous vasculature of the patient, and a first wireless interface configured to wirelessly transmit the endovascular electrogram signal to the processor. The processor includes a second wireless interface configured to wirelessly receive the endovascular electrogram signal from the elongate flexible member. The processor is configured to determine that the position of the distal end of the elongate flexible member is within a predetermined structure within the venous vasculature of the patient. The display is configured to display a visual indication that the distal end of the elongate flexible member is within the predetermined structure within the venous vasculature of the patient.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/331,899 (filed Oct. 23, 2016), which is a continuation of U.S. patentapplication Ser. No. 15/009,745 (filed Jan. 28, 2016 and now U.S. Pat.No. 10,321,890), which is a continuation of U.S. patent application Ser.No. 13/844,408 (filed Mar. 15, 2013 and now abandoned), which is acontinuation of U.S. patent application Ser. No. 12/147,401 (filed Jun.26, 2008 and now U.S. Pat. No. 8,597,193), which claims the benefit ofU.S. Provisional Patent App. No. 60/937,280 (filed Jun. 26, 2007 and nowexpired), U.S. Provisional Patent App. No. 60/957,316 (filed Aug. 22,2007 and now expired), and U.S. Provisional Patent App. No. 61/023,183(filed Jan. 24, 2008 and now expired). U.S. patent application Ser. No.12/147,401 is also a continuation-in-part of U.S. patent applicationSer. No. 11/431,140 (filed May 8, 2006 and now U.S. Pat. No. 9,204,819),U.S. patent application Ser. No. 11/431,118 (filed May 8, 2006 and nowU.S. Pat. No. 9,198,600), U.S. patent application Ser. No. 11/431,093(filed on May 8, 2006 and now abandoned), and U.S. patent applicationSer. No. 11/430,511 (filed May 8, 2006 and now U.S. Pat. No. 8,409,103),all of which claim the benefit of U.S. Provisional Patent App. No.60/678,209 (filed May 6, 2005 and now expired) and U.S. ProvisionalPatent App. No. 60/682,002 (filed May 18, 2005 and now expired). Each ofthese applications and patents is incorporated herein by reference inits entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

BACKGROUND

The invention relates to the guidance, positioning and placementconfirmation of intravascular devices, such as catheters, stylets,guidewires and other elongate bodies that are typically insertedpercutaneously into the venous or arterial vasculature, includingflexible elongate bodies. Currently these goals are achieved using x-rayimaging and in some cases ultrasound imaging. This invention provides amethod to substantially increase the accuracy and reduce the need forimaging related to placing an intravascular catheter or other device.Reduced imaging needs also reduce the amount of radiation that patientsare subjected to, reduce the time required for the procedure, anddecrease the cost of the procedure by reducing the time needed in theradiology department.

The vasculature of mammals has long been accessed to provide therapy,administer pharmacological agents and meet other clinical needs.Numerous procedures exist in both venous and arterial systems and areselected based on patient need. One challenge common to allvascular-based therapies is health care provider access to the specificlocation or section of the vascular tree.

One common venous access procedure is central venous access. Centralvenous access is the placement of a venous catheter in a vein that leadsdirectly to the heart. Central venous catheters are ubiquitous in modernhospital and ambulatory medicine, with up to 8 million insertions peryear in the U.S. and a similar number outside the U.S.

Venous access devices are most often used for the following purposes:

-   -   Administration of medications, such as antibiotics, chemotherapy        drugs, and other IV drugs    -   Administration of fluids and nutritional compounds        (hyperalimentation)    -   Transfusion of blood products    -   Hemodialysis    -   Multiple blood draws for diagnostic testing.

Central venous access devices are small, flexible tubes placed in largeveins for people who require frequent access to their bloodstream. Thedevices typically remain in place for long periods: week, months, oreven longer.

Central venous access devices are usually inserted in 1 Cof 3 ways:

-   -   a) Directly via a catheter. Catheters are inserted by tunneling        under the skin into either the subclavian vein (located beneath        the collarbone) or into the internal jugular vein (located in        the neck). The part of the catheter where medications are        administered or blood drawn remains outside of the skin.    -   b) Through a port. Unlike catheters, which exit from the skin,        ports are placed completely below the skin. With a port, a        raised disk about the size of a quarter or half dollar is felt        underneath the skin. Blood is drawn or medication delivered by        placing a tiny needle through the overlying skin into the port        or reservoir.    -   c) Indirectly via a periphal vein. Peripherally inserted central        catheter (PICC) lines, unlike central catheters and ports, are        not inserted directly into the central vein. A PICC line is        inserted into a large vein in the arm and advanced forward into        the larger subclavian vein.

Central catheters and ports are usually inserted by a surgeon orsurgical assistant in a surgical suite. An alternative is placementunder the guidance of a special x-ray machine so that the personinserting the line can make sure that the line is placed properly. APICC line can be put in at bedside, usually by a specially trainednurse. In this later case, confirmation by X-ray is currently requiredfor assessing the success of the PICC placement.

Traditional surgically placed central catheters are increasingly beingreplaced by peripherally inserted central venous access devices. PICClines usually cause fewer severe complications than central venousaccess devices. Peripherally-Inserted-Central-Catheter (PICC) is used ina variety of clinical procedures. The PICC line placement procedure isperformed by interventional radiologists to deliver long-term drugdelivery, chemotherapy procedures, delivery of intravenous medicationsor intravenous nutrition (hyperalimentation) and taking blood samplesvia a Hickman catheter. Insertion of PICC lines is a routine procedurein that it is carried out fairly often for a variety of treatments, andmore than once in the same patient when the catheter is to be left inplace for any length of time. Even though it is routine, it is a verytime and labor-intensive procedure for the hospital staff, which alsomakes it expensive. During the procedure the physician or nurse placesthe catheter into a superficial arm vein such as the cephalic, basilic,antecubital, median cubital, or other superficial vein with the goal ofhaving the distal end of the catheter reach the superior vena cava.After entering the superficial vein around the area where the arm bends(elbow), the catheter is advanced up the subclavian vein, then thebrachiocephalic vein and finally it enters the superior vena cava. Onecaveat is to make sure that the PICC line does not enter the jugularvein via the subclavian vein.

Hemodialysis therapy via a hemodialysis catheter is another example of aprocedure requiring central venous access. A dialysis catheter is aspecialized type of central venous catheter used for dialysis. Dialysiscatheter placement involves the insertion of a catheter into a largevessel, utilizing X-ray guidance. The challenges of inserting ahemodialysis catheter in terms of guidance and positioning are similarto those of a central venous catheter, only they are typically largerand require a peel-away sheath for insertion.

Another therapy achieved via providing access to the venous system isthe percutaneous treatment of varicose veins. Published populationstudies indicate that approximately 25 million people in the U.S. and 40million people in Western Europe suffer from symptomatic venous refluxdisease. Percutaneous treatment of varicose veins involves the placementof an energy delivery catheter (laser or RF) after navigation thevasculature to locate the treatment site. One common treatment site isthe sapheno-femoral junction and less common sites are thesapheno-popliteal junction and sites of perforator veins, which connectthe superficial venous system to the deep venous system of the leg at avariety of different locations, mostly below the knee. As such, in thecase of percutaneous treatment of varicose veins using specific venousjunctions, the position the laser or the RF catheter at an optimallocation with respect to the venous junction is critical for the successof the intervention.

In addition to guiding the catheter through the vasculature, thelocation of the catheter tip is very important to the success of theprocedure. Catheters will generally function equally well for pressuremeasurement and fluid infusion if the tip is situated in any major vein,above or below the heart. For dialysis or the infusion ofirritant/hypertonic fluids, a high rate of blood flow past the cathetertip is desirable and this requires the placement of the luminal openingin as large a vessel as possible. However, the package inserts of manycentral venous catheters give very strong warnings about the absoluterequirement for catheter tips to lie outside the heart to avoidperforation and subsequent pericardial tamponade. Likewise positioningthe catheter tip away from small peripheral veins is important to avoiddamaging the vein wall or occluding the vein due the caustic effects ofthe infusing solution. It is also of major interest that the cathetertip stays in place after placement for the whole duration of thetreatment. If the catheter tip moves, not only its effectivenessdiminished but, in some situations, it can perforate the heart. In theUnited States, the Food and Drug Administration has issued adviceemphasizing this point. Typically, the interventional radiologist uses afluoroscopic agent to delineate the veins in the body and subsequentlyverifies the correct positioning of the catheter tip using apost-operative X-ray. Currently, post-operative X-ray is performedroutinely while some studies have shown that only 1.5% of the cases aresubject to complications that would indeed require X-ray imaging.

Current methods for guiding PICC lines include external electromagneticsensors and intravascular, e.g, ECG. N the case of electromagneticsensors, the endovascular device is guided by assessing the distancebetween an electromagnetic element at the tip of the device, e.g., acoil and an external (out of body) receiver. This method is inaccuratebecause it does not actually indicate location in the vascular butdistance to an outside reference. In the case of ECG-guided catheters,the classic increase in P-wave size, known as ‘P-atriale”, is a widelyaccepted criterion for determining location of central venous cathetertips in the proximity of the sino-atrial node. Current methods includeusing a catheter filled with saline and an ECG adaptor at the proximalend connected to an ECG system. This method is inaccurate because itdoes not indicate location in the blood vessel but the proximity of thesino-atrial node. Because of known inaccuracies, all the current methodsin use do explicitly require the use of a confirmatory chest X-ray toverify and confirm location of the tip of the endovascular device at thedesired target in the vasculature. Most prior art relating to the use ofintravascular ultrasound or electrical mapping of heart activity fordiagnostic and therapeutic purposes addresses problems independently:some addresses ultrasound guidance on the arterial side such as thatdescribed by Franzin in Doppler-guided retrograde catheterization usingtransducer equipped guide wire (U.S. Pat. No. 5,220,924) or thatdescribed by Katims in Method and apparatus for locating a catheteradjacent to a pacemaker node of the heart (U.S. Pat. No. 5,078,678).Such approaches have intrinsic limitations which does not make themsuited to solve the problem addressed by the current invention. Thelimitations of the Frazin approach have been extensively explained inVasoNova patent applications US 20070016068, 20070016069, 20070016070,and 20070016072. Limitations of an approach based exclusively onmeasuring right-atrial electrocardiograms have been described in theliterature, for example in [1]: W. Schummer et al., Central venouscatheters—the inability of ‘intra-atrial ECCG’ to prove adequatepositioning, British Journal of Anaesthesia, 93 (2): 193-8, 2004.

What is needed are methods and apparatuses to optimize guidance andplacement of catheters in order to reduce the risk associated with wrongplacement and the cost associated with the X-ray imaging. Further thereremains a need for a catheter guidance and placement system that may beused to safely guide and place catheters in healthcare provider orclinical environments other than in the radiology department or surgicalsuite wherein a radiological or other external imaging modality is usedto confirm catheter placement. As such, there remains a need in themedical arts for instruments, systems and associated methods forlocating, guiding and placing catheters and other instruments into thevasculature generally. In addition remains a need in the medical artsfor instruments, systems and associated methods for locating, guidingand placing catheters and other instruments into the vasculature to meetthe challenges presented by the unique characteristics and attributesspecific to the vascular system of interest. The current inventionovercomes the above described limitations by making use of physiologicalparameters like blood fow and ECG measured in the vasculature and isbased on the fact that physiological parameters and their relationshipis unique to the locations in the vasculature where the endovasculardevices needs to be placed. The current invention describes an apparatusfor identifying the unique physiological signature of a certain locationin the vasculature and a method to guide the endovascular device to thatlocation based on the physiological signatures.

SUMMARY OF THE DISCLOSURE

An aspect of the invention includes an endovenous access and guidancesystem. The system comprises: an elongate flexible member adapted andconfigured to access the vasculature of a patient; sensors disposed at adistal end of the elongate flexible member and configured to provideintravascular electrocardiogram signals and blood flow velocity profileinformation of the vasculature of the patient using in vivo non-imagebased ultrasound or near infrared light, temperature measurements,pressure measurements and other types of sensors and measurements whichcan provide blood velocity information, a processor configured toreceive, process, and correlate blood flow velocity information andintravascular electrocardiogram signals of the vasculature of thepatient provided by the sensors and to provide position informationregarding the position of the distal end of the elongate flexible memberwithin the vasculature of the patient; and an output device adapted tooutput the position information from the processor. In some embodiments,the elongate flexible member is further adapted to provide a catheter, aguidewire, and/or a stylet. In other embodiments, the device is adaptedto deliver therapy to a patient, or provide vascular access for anotherdevice. In still another embodiment, the system is adapted to furthercomprise a sensor attachment mechanism adapted to removably detach thesensors from the elongate flexible member while the elongate flexiblemember remains in the vasculature of the patient. In yet anotherembodiment, the system is configured such that the processor processesin vivo non-image based ultrasound information and intravascularelectrocardiogram signals of the vasculature system of the patientprovided by the sensors to indicate in the output information theproximity of the sensors to a structure within the vasculature of thepatient. In still other embodiments, the processor can be furtherconfigured to process in vivo non-image based ultrasound information andintravascular electrocardiogram signals of the vasculature system of thepatient to indicate in the output information movement of the elongateflexible member in a desired direction within the vasculature of thepatient. Alternatively, the processor is further configured to processin vivo non-image based ultrasound information and intravascularelectrocardiogram signals of the vasculature system of the patient basedon a parameter selected from a group consisting of: a blood flowdirection, a blood flow velocity, e.g., the highest, the lowest, themean or the average velocity, a blood flow signature pattern, a pressuresignature pattern, A-mode information, a preferential non-randomdirection of flow, the shape of the different waveforms and complexescharactering the intravascular electrocardiogram, e.g., P-wave, QRScomplex, T-wave, the peak-to-peak amplitudes, the absolute and relativeamplitude changes and other distinctive elements of the intravascularECG. Such parameters can be used either individually or in combinationin order to increase the reliability of detecting locations in thevasculature based on functional behavior and physiological parametersmeasurements, for example the P-wave changes indicative or the proximityof the sinoatrial node near the caval-atrial junction and together withthe venous blood flow signature pattern indicative of the caval-atrialjunction. Furthermore, the behavior of such parameters in time is alsoindicative of location in the vasculature, e.g. evident pulsatilevariations of the blood flow signature pattern may be indicative of alocation in the internal jugular vein. In another aspect of theinvention, the system further comprises a catheter, stylet, or guidewireelectrode for recording intravascular electrocardiograms which can alsobe used as a mechanism for steering, centering, and separating theendovascular member away from the vessel wall.

Another aspect of the invention includes a method for positioning aninstrument in the vasculature of a body. The method comprises the stepsof: accessing the vascular system of the body; positioning an instrumentin the vascular system of the body; using the instrument to transmit anultrasound signal into the vascular system of the body; using theinstrument to receive a reflected ultrasound signal from the vasculatureindicating flow rates between 2 and 20 cm/s; using the instrument tomeasure intravascular electrical activity of the heart, processing thereflected ultrasound and electrocardiogram signals to determine one ormore parameters and their temporal behavior from a group consisting of:a blood flow direction, a blood flow velocity, e.g., the highest, thelowest, the mean or the average velocity, a blood flow signaturepattern, a pressure signature pattern, A-mode information, apreferential non-random direction of flow, the shape of the differentwaveforms and complexes charactering the intravascularelectrocardiogram, e.g., P-wave, QRS complex, T-wave, the peak-to-peakamplitudes, the absolute and relative amplitude changes and otherdistinctive elements of the intravascular ECG; and advancing theinstrument within the vasculature using the one or more of thedetermined parameter or parameters within the vasculature. In yet otherembodiments, processing the reflected ultrasound signal and theintravascular or intracardiac electrocardiogram signal and theircorrelation to determine the position of the instrument relative to thecaval-atrial junction and other specific location within the body isperformed. In other aspects of the invention, the specific targetvasculature for positioning an instrument is included, for example, thespecific structure is a valve of a heart, a blood vessel wall, a heartwall, a pacemaker node of the heart. In another aspect of the invention,the method can further comprise identifying a certain obstructingstructure in a blood vessel or within the lumen of an endovasculardevice which can obstruct either the advancement of the endovasculardevice in the blood vessel or the delivery of a payload through a lumenof the devices, e.g., a blood clot In another aspect of the invention,the method can further comprise: using the instrument determine alocation to secure a device within the vasculature of a body; andsecuring the device to the body to maintain the device in the locationdetermined by the instrument. In still another aspect of the method, themethod can further comprise: using the instrument to calculate thecurrent position of the device; and determining if the device is in thelocation determined by the instrument by comparing the currentcalculated position of the device to the location determined by theinstrument. In some aspects of the method, the method further comprisesprocessing the reflected ultrasound signal and the intravascular orintracardiac electrocardiogram to determine the position of theinstrument within the lower third of the superior vena cava. In stillother aspects the method further comprising processing the reflectedultrasound signal and the intravascular or intracardiacelectrocardiogram to determine the position of the instrument within theright atrium relative to the coronary sinus. In still other aspects, themethod further comprising processing the reflected ultrasound signal andthe intravascular or intracardiac electrocardiogram to determine theposition of the instrument within the left atrium relative to apulmonary vein. In one embodiment, the methods described above comprisethe following steps: 1. The sensor-based endovascular devices having atleast a Doppler sensor and an intravascular ECG sensor is placed in thevasculature of the patient through a vascular access site. A baselineECG and a baseline blood velocity profile are captured in the bloodvessel at location A1 and displayed and/or stored by the system.Specifically one or more of the following physiological measurements areconsidered: the blood velocity profile, the highest, the lowest, themean or the average blood velocity, the P-wave amplitude, theQRS-complex amplitude and the ratio between the P-wave and theQRS-complex amplitudes, 2. The sensor-based endovascular device isadvanced to a location A2 in the vasculature and the same parameters areagain analyzed which have been analyzed at location A1. 3. Severalalgorithms are then applied to compare the information at location A2with the information at location A1 as described in the presentinvention. 4. In addition, the information at location A2 can becompared against information contained in a knowledge base regarding therelationship between such information and locations in the vasculature,as further described in the present invention. 5. Decision criteria arethen applied to the processed information in order to establishcorrelation with the anatomical location as further described in thepresent invention. In another embodiment, the P-wave and/or the QRScomplex of the ECG can be used to gate the acquisition/and or analysisof the blood flow velocity information in order to restrict the analysisto only a segment of the heart cycle and thus increase reliability ofinformation and accuracy of location identification.

In one embodiment of the invention, there is an endovascular access andguidance system including some or all of the following components: anelongate body with a proximal end and a distal end; a non-imagingultrasound transducer on the elongate body configured to provide in vivonon-image based ultrasound information of the vasculature of thepatient; an endovascular electrogram lead on the elongate body in aposition that, when the elongate body is in the vasculature, theendovascular electrogram lead electrical sensing segment provides an invivo electrogram signal of the patient; a processor configured toreceive and process a signal from the non-imaging ultrasound transducerand a signal from the endovascular electrogram lead; and an outputdevice configured to display a result of information processed by theprocessor.

These components may be modified or removed depending upon the specificapplication of a guidance system. The output device may display a resultrelated to a position of the elongate body within the vasculature of thepatient. The processor may be configured to process a signal from thenon-image ultrasound transducer and to indicate in the output deviceinformation related to the presence of a structure in the field of viewof the non-imaging ultrasound transducer. A result of informationprocessed by the processor comprises: an indication of a position or amovement of the elongate body within the vasculature based on in vivonon-image based ultrasound information and in vivo electrograminformation.

The endovascular access and guidance system may also include a drivercoupled to the ultrasound transducer adapted to drive the ultrasoundtransducer in response to an electrogram signal. The driver coupled tothe ultrasound transducer is adapted to drive the ultrasound transducerin a plurality of ultrasound transmission modes.

The endovascular access and guidance system may also include a secondendovascular electrogram lead on the elongate body positioned distal tothe endovascular electrogram lead wherein the processor is furtherconfigured to receive and process a signal from the second endovascularelectrogram lead. In addition, the processor is further configured tocompare the signal from the endovascular electrogram lead and the secondendovascular electrogram lead. In one aspect, the signal from theendovascular electrogram lead includes a target electrogram signal andthe second endovascular electrogram lead comprises a baselineelectrogram signal. In one aspect, the target electrogram signal and thebaseline electrogram signal are related to ECG, to EMG or to EEG, aloneor in any combination.

The endovascular access and guidance system may also include anadditional sensor for detecting a physiological parameter of thevasculature, the sensor positioned along the elongate body. Theprocessor may also be configured to receive and process a signal fromthe additional sensor. The additional sensor for detecting aphysiological parameter of the vasculature may be, for example, apressure sensor or an optical sensor.

The processor may also be configured to receive and process a signalfrom the non-imaging ultrasound transducer comprising a signal from atleast one of the group consisting of: a venous blood flow direction, avenous blood flow velocity, a venous blood flow signature pattern, apressure signature pattern, A-mode information and a preferentialnon-random direction of flow and to receive and process a signal fromthe endovascular electrogram lead the signal comprising at least one ofthe group consisting of: an electrocardiogram signal, a P-wave pattern,a QRS-complex pattern, a T-wave pattern, an EEG signal and an EMGsignal.

In still another aspect, the endovascular access and guidance system hasa processor configured to store a signal received from the non-imagingultrasound transducer and a signal received from the endovascularelectrogram lead. The processor may also be configured to process aportion of the stored signal received from the non-imaging ultrasoundtransducer that corresponds to a signal received from the endovascularelectrogram lead. The signal received from the endovascular electrogramlead comprised a P-wave.

According to one aspect of the invention, an endovascular deviceincludes an elongate body with a proximal end and a distal end; anon-imaging ultrasound transducer on the elongate body; and anendovascular electrogram lead on the elongate body in a position that,when the endovascular device is in the vasculature, the endovascularelectrogram lead is in contact with blood. In one aspect, theendovascular electrogram lead is positioned at the elongate body distalend. Additionally or alternatively, the electrical sensing segment of anendovascular electrogram lead is positioned: within 3 cm of the elongatebody distal end; within 3 cm of the non-imaging ultrasound transducer;and/or proximal to the non-imaging ultrasound transducer.

In an alternative of the endovascular device, the device also includes asecond endovascular electrogram lead on the elongate body in a positionthat, when the endovascular device is in the vasculature, the secondendovascular electrogram lead is in contact with blood. Additionally oralternatively, the electrical sensing segment of the second endovascularelectrogram lead is positioned about 5 cm from the endovascularelectrogram lead or positioned about 5 cm from the elongate body distalend.

In other embodiments of the endovascular device, the electrical sensingsegment of the second endovascular electrogram lead is positioned at adistance spaced apart from the endovascular electrogram lead so that thesecond endovascular electrogram lead detects a baseline electrogramsignal when the endovascular electrogram lead is detecting a targetelectrogram signal; at a distance related to the length of the superiorvena cava such that when the endovascular electrogram lead is in thesuperior vena cava the second endovascular electrogram lead is outsideof the superior vena cava; such that when the electrical sensing segmentof the endovascular electrogram lead is positioned to detect a targetedelectrogram signal from the heart the electrical sensing segment of thesecond endovascular electrogram lead is positioned to detect acomparison baseline ECG signal; such that when the electrical sensingsegment of the endovascular electrogram lead is positioned to detect atargeted electrogram signal from the brain the electrical sensingsegment of the second endovascular electrogram lead is positioned todetect a comparison baseline EEG signal; and/or such that when theelectrical sensing segment of the endovascular electrogram lead ispositioned to detect a targeted electrogram signal from a muscle theelectrical sensing segment of the second endovascular electrogram leadis positioned to detect a comparison baseline EMG signal.

In other aspects of the endovascular device, the endovascularelectrogram lead is moveable from a stowed condition within the elongatebody and a deployed condition outside of the elongate body. In onealternative, the stowed endovascular electrogram lead curves the distalend of the endovascular device. Additionally, when the endovascularelectrogram lead is in the stowed condition the electrical sensingsegment is positioned to detect an electrogram signal.

One embodiment of the endovascular device may also include a steeringelement connected to the endovascular lead for directing the proximalend of the elongate body and the steering element may also providetorque to the elongate body distal end.

One embodiment of the endovascular electrogram lead in use extends atleast partially about the elongate body and may include and anatraumatic tip. In one aspect, the endovascular device has anendovascular electrogram lead that is formed from a shape memory alloy.Additionally or alternatively, the endovascular electrogram lead isadapted for use to move the ultrasound sensor away from a blood vesselwall.

In another alternative, the endovascular device includes a coated metalbraided structure and a portion of the coating on the metal braidedstructure is removed and the exposed metal braided structure functionsas an endovascular electrogram lead electrical sensing segment.

In another alternative, the endovascular device includes an atraumatictip on the distal end of the endovascular device. In one aspect, theatraumatic tip comprises an ultrasound lens and the lens may, forexample, be a divergent lens.

The endovascular device may also include an opening in the elongatebody; and a lumen within the elongate body in communication with theopening and the elongate body proximal end.

The endovascular device may also include an additional sensor on theendovascular device for measuring a physiological parameter. Theadditional sensor is an optical sensor for use when the physiologicalparameter is related to an optical property detected within thevasculature. The additional sensor is a pressure sensor for use when thephysiological parameter is related to a pressure measurement obtainedwithin the vasculature. The additional sensor is an acoustic sensor foruse when the physiological parameter is related to an acoustic signaldetected within the vasculature.

The elongate flexible member may be configured as or to work incooperation with an endovascular device such as, a catheter, a guidewire, or a stylet.

Moreover, the elongate flexible member may also be adapted to deliver atherapy to the patient and/or adapted to provide endovascular access foranother device.

In one aspect, the method of positioning an endovascular device in thevasculature of a body is accomplished by advancing the endovasculardevice into the vasculature and then transmitting a non-imagingultrasound signal into the vasculature using a non-imaging ultrasoundtransducer on the endovascular device. Next, there is the step ofreceiving a reflected ultrasound signal with the non-imaging ultrasoundtransducer and then detecting an endovascular electrogram signal with asensor on the endovascular device. Then there is the step of processingthe reflected ultrasound signal received by the non-imaging ultrasoundtransducer and the endovascular electrogram signal detected by thesensor. Finally, there is the step of positioning the endovasculardevice based on the processing step.

The method of positioning an endovascular device in the vasculature of abody may also include additional or modified steps according to thespecific application or process being performed. Numerous additionalalternative steps are possible and may be used in a number ofcombinations to achieve the guidance and positioning results describedherein. Additional steps may include verifying that the length of theendovascular device inserted into the body is equivalent to theestimated device length prior to the procedure and/or inputting into thesystem the length of the endovascular device inserted in the body.Additionally, the step of detecting an endovascular electrogram signalwith a sensor positioned on a patient may be added. The sensor may be onthe patient or a second or additional sensor on an endovascular device.There may also be added the step of comparing the endovascularelectrogram signal from the sensor on the device or patient to theendovascular electrogram signal from the second sensor on the device.

The processing methods and algorithms may also be modified or combinedto identify important or unique signatures useful in guidance,localization or correlation. The method may include different orcustomized software or programming for processing ultrasound and/orelectrogram signal information. The processing may include processing ofreflected ultrasound signal to identify the caval-atrial junction or todetermine the highest average velocity of a velocity profile. Theprocessing may include processing of the endovascular electrogram signalto determine: peak to peak amplitude changes in an electrogram complex;peak to peak amplitude changes of an QRS complex in anelectrocardiogram; peak to peak amplitude changes of an R-wave in anelectrocardiogram and or peak to peak amplitude changes of an P-wave inan electrocardiogram and, additionally or alternatively, to useelectrogram information as a trigger to acquire and/or processultrasound information.

The processing methods and algorithms may also be modified or combinedto identify important or unique signatures to determine the position ofa guided endovascular device relative to anatomical structures orpositions in the body. Examples of these methods include performing theprocessing step to determine the position of the endovascular devicerelative to: the caval-atrial junction, the sinoatrial node, thesuperior vena cava, the internal jugular vein, and the subclavian vein.

The method of positioning an endovascular device in the vasculature of abody may be further modified to include using the endovascular device todetermine a location to secure a device within the vasculature of a bodyand then securing the endovascular device along with the device to thebody to maintain the device in the location determined by theendovascular device. The method of positioning an endovascular device inthe vasculature of a body may also include the steps of calculating acurrent position of the device and then comparing the calculated currentposition of the device to a location indicated by the processing step.

The steps of the method may be performed in any order or repeated inwhole or in part to achieve the desired positioning or placement of theguided endovascular device. For example, the method of positioning anendovascular device in the vasculature of a body may include performingthe processing step and the positioning step until the endovasculardevice is positioned within the right atrium relative to the coronarysinus. Alternatively, the method of positioning an endovascular devicein the vasculature of a body may include performing the processing stepand the positioning step until the endovascular device is positionedwithin the left atrium relative to a pulmonary vein. Alternatively, themethod of positioning an endovascular device in the vasculature of abody may also include performing the processing step and the positioningstep until the endovascular device is positioned within the aorta.

This aspect may be modified to include, for example, an additional stepof displaying a result of the processing step. The processing step mayalso include information related to venous blood flow direction. Thevenous flow direction may also include a flow directed towards thesensor and a flow directed away from the sensor. Additionally oralternatively, the result of the processing step may also include one ormore of information related to venous blood flow velocity, informationrelated to venous blood flow signature pattern, information related to apressure signature pattern, information related to ultrasound A-modeinformation; information related to a preferential non-random directionof flow within a reflected ultrasound signal, information related toelectrical activity of the brain, information related to electricalactivity of a muscle, information related to electrical activity of theheart, information related to the electrical activity of the sinoatrialnode; and information about the electrical activity of the heart from anECG.

In another aspect, the displaying step may also be modified to include avisual indication of the position of the device. The displaying step mayalso be modified to include a visual or color based indication of theposition of the device alone or in combination with a sound basedindication of the position of the device.

The method of positioning an endovascular device in the vasculature of abody may also be modified to include the step of collecting thereflected ultrasound signal in synchrony with an endovascularelectrogram signal received by the sensor. Additional alternatives arepossible such as where the endovascular electrogram comprises electricalactivity from the heart, from the brain or from a muscle. The collectionstep may be timed to correspond to physiological actions or timings. Forexample, the collecting step is performed in synchrony during the PRinterval or in synchrony with a portion of the P-wave.

Other portions of an EEG, ECG or EMG electrogram may also be used fortiming of collecting, processing and/or storing information from devicebased or patient based sensors. In one aspect of the method ofpositioning an endovascular device in the vasculature of a body, thetransmitting step, the receiving step and the processing step areperformed only when a selected endovascular electrogram signal isdetected. In one version of the method, the selected endovascularelectrogram signal is a portion of an ECG wave. In another version ofthe method, the selected endovascular electrogram signal is a portion ofan EEG wave. In still another version of the method, the selectedendovascular electrogram signal is a portion of an EMG wave.

The method of positioning an endovascular device in the vasculature of abody may also include identifying a structure in the vasculature usingnon-imaging ultrasound information in the reflected ultrasound signal.In one aspect, the non-imaging ultrasound information comprises usingA-mode ultrasound to identify the structure in the vasculature. Inanother aspect, the non-imaging ultrasound information includes usingDoppler ultrasound information to identify a flow pattern in proximityto the structure.

An another aspect of the method of positioning an endovascular device inthe vasculature of a body the processing step is performed only on aportion of the reflected ultrasound signals that correspond to aselected electrogram trigger signal. This method may be employed, forexample, when the selected electrogram trigger signal is a portion of anECG wave, a portion of an EEG wave or a portion of an EMG wave.

In still other methods of positioning an endovascular device in thevasculature of a body, the processing step may be modified to includeprocessing the reflected ultrasound signal by comparing the flow energydirected away from the endovascular device to the flow energy directedtowards the endovascular device. In one aspect, there is a step ofselecting for comparison the flow energy related to blood flow withinthe range of 2 cm/sec to 25 cm/sec.

In still other alternatives, the method of positioning an endovasculardevice in the vasculature of a body includes a processing step that hasa step of processing the reflected ultrasound signal to detect anindicia of pulsatile flow in the flow pattern. The indicia of pulsatileflow may be any of a number of different parameters. The indicia ofpulsatile flow may be: a venous flow pattern; an arterial flow patternor an atrial function of the heart.

The method of positioning an endovascular device in the vasculature of abody may also include modification to the processing step to include thestep of processing the endovascular electrogram signal to compare therelative amplitude of a P-wave to the relative amplitude of anotherportion of an electrocardiogram. In one aspect, the another portion ofan electrocardiogram includes a QRS complex. The processing step mayalso be modified to include processing the reflective ultrasound signalto determine a blood flow velocity profile and processing the detectedendovascular electrogram signal to determine a shape of theintravascular electrocardiogram. The processing step may be furthermodified to include the step of correlating the blood flow velocityprofile and the shape of the intravascular electrocardiogram todetermine the location of the endovascular device within thevasculature.

In one aspect, there is an endovascular access and guidance system withone or more of the following components:

an elongate flexible member adapted and configured to access thevasculature of a patient; a sensor disposed at a distal end of theelongate flexible member and configured to provide in vivo non-imagebased ultrasound information of the vasculature and of the heart of thepatient; a sensor disposed at a distal end of the elongate flexiblemember and configured to provide in vivo electrical signals(electrocardiograms) of the vasculature and of the heart of the patient;a processor configured to receive and process in vivo non-image basedultrasound information and electrocardiogram information of thevasculature and the heart of the patient provided by the sensors and toprovide position information regarding the position of the distal end ofthe elongate flexible member within the vasculature and the heart of thepatient; and/or an output device adapted to output the positioninformation from the processor.

In one configuration, the processor used in the endovascular access andguidance system is configured or programmed to perform one or more ofthe following:

process in vivo non-image based ultrasound information of thevasculature system of the patient provided by the sensor to indicate inthe output information the presence of structures and objects in thefield of view; process in vivo non-image based ultrasound informationand the electrocardiogram information of the vasculature system of thepatient to indicate in the output information movement of the elongateflexible member in a desired direction within the vasculature of thepatient; and process in vivo non-image based ultrasound information ofthe vasculature system of the patient based on a parameter selected froma group consisting of: a venous blood flow direction, a venous bloodflow velocity, a venous blood flow signature pattern, a pressuresignature pattern, A-mode information and a preferential non-randomdirection of flow, electrocardiogram signals, P-wave pattern,QRS-complex pattern, T-wave pattern.

The endovascular access and guidance system may include two or moreadditional sensors wherein the sensor and the two or more additionalsensors are attached to the elongate flexible member to allow formeasurements at different locations along the flexible member. Theendovascular access and guidance system may also have a steering elementfor directing the device tip in response to feedback information derivedfrom the acquired data. The endovascular access and guidance system mayalso have a torque control element for directing the device tip inresponse to feedback information derived from the acquired data.

In one aspect, there is a method for positioning an instrument in thevasculature system of a body by performing one or more or some of thesteps of: accessing the vasculature of the body; positioning aninstrument in the vasculature of the body; using the instrument totransmit an ultrasound signal into the venous system of the body; usingthe instrument to receive a reflected ultrasound signal from thevasculature indicating flow rates between 2 and 20 cm/s; using theinstrument to record endovascular electrocardiograms indicating theproximity of the sinoatrial node of the heart; processing the reflectedultrasound signal and electrocardiogram to determine one or moreparameters from a group consisting of: a venous blood flow direction, avenous blood flow velocity, a venous blood flow signature pattern, apressure signature pattern, A-mode information and a preferentialnon-random direction of flow, electrocardiogram signals, P-wave pattern,QRS-complex pattern, T-wave pattern; and advancing the instrument withinthe vasculature using the one or more of the determined parameter orparameters within the vasculature.

The method for positioning an instrument in the vasculature of a bodymay also be modified or adjusted to include one or more of the steps of:transmitting or receiving an A mode ultrasound signal into or from thevasculature of the body using the instrument that is being positioned;transmitting or receiving Doppler ultrasound signal into or from thevasculature of the body; transmitting or receiving a non-imaging targettracking ultrasound signal into or from the vasculature of the body;recording endovascular and intracardiac electrocardiograms from thevasculature of the body using the instrument; processing the reflectedultrasound signal and the endovascular electrocardiogram to determine aflow pattern determines a flow direction within the vasculature towardsthe instrument and further comprises processing the reflected ultrasoundsignal to determine a flow pattern determines a flow direction away fromthe instrument; processing the reflected ultrasound signal and theendovascular electrocardiogram to determine the presence of a signalindicating a specific blood flow pattern and a specificelectrocardiogram pattern; processing the reflected ultrasound signaland the endovascular electrocardiogram and the endovascularelectrocardiogram to determine the position of the instrument relativeto the caval-atrial junction and to the sinoatrial node; processing thereflected ultrasound signal to determine the presence of a signalindicating a specific structure, including when the specific structureis a blood clot; processing the reflected ultrasound signal and theendovascular electrocardiogram and the endovascular electrocardiogram todetermine the position of the instrument relative to the internaljugular vein; processing the reflected ultrasound signal and theendovascular electrocardiogram and the endovascular electrocardiogram todetermine the position of the instrument relative to the subclavianvein; determining a location to secure a device within the vasculatureof a body using information collected by the instrument; and securingthe device to the body to maintain the device in the determinedlocation; calculating the current position of the device usinginformation from the instrument; and determining, based on thecalculating step, if the device is in the location determined by theinstrument by comparing the current calculated position of the device tothe location determined by the instrument; processing the reflectedultrasound signal and the endovascular ECG to determine the position ofthe instrument within the right atrium relative to the coronary sinus;and/or processing the reflected ultrasound signal and the endovascularECG to determine the position of the instrument within the left atriumrelative to a pulmonary vein.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1 illustrates an overview of the endovascular device guidingapparatus and method disclosed in the present invention.

FIG. 2 illustrates an endovascular device with multiple sensors.

FIG. 3A-3B illustrates an intravascular ECG electrode which can be usedfor steering and moving the endovascular member away from the vesselwall.

FIG. 4A-4C illustrates the concept of removable sensor core, whereby astylet with integrated sensors can be inserted into and removed from anendovascular device like a catheter at any time.

FIG. 5A-5B illustrates an embodiment integrated sensors in anendovascular device with braided shaft and atraumatic tip.

FIG. 6 illustrates another embodiment of integrated sensors in anendovascular device with stylet-like reinforcement that can be used asan ECG electrode.

FIG. 7 illustrates the flow velocity profiles, the intravascular ECGsignal and their correlation as detected by the device according to thepresent invention in the superior vena cava as documented by thesynchronized fluoroscopic image.

FIG. 8 illustrates the flow velocity profiles, the intravascular ECGsignal and their correlation as detected by the device according to thepresent invention at the caval-atrial junction as documented by thesynchronized fluoroscopic image.

FIG. 9 illustrates the flow velocity profiles, the intravascular ECGsignal and their correlation as detected by the device according to thepresent invention in the internal jugular vein as documented by thesynchronized fluoroscopic image.

FIG. 10 illustrates the use of intravascular ECG signal to gate ortrigger the acquisition or processing of the blood flow information.

FIG. 11 illustrates the effect of using additional gating based onpatient's breathing on the acquisition and processing of blood flowinformation.

FIG. 12 illustrates the use of intravascular ECG signals in case ofa-fib patients.

FIG. 13 illustrates a graphical user interface displaying blood flowinformation, intravascular ECG signals, their correlation, and cathetertip location information based on the above. FIG. 13 also illustratesthe use of A-mode imaging for clot identification inside the bloodstream or inside an endovascular member.

FIG. 14A-14D illustrates a simplified user interface using blood flowinformation, intravascular ECG signals and their correlation to displayif the endovascular member is advancing towards the caval-atrialjunction and sinoatrial node, if the endovascular member is advancingaway from the caval-atrial junction and sinoatrial node, or if theendovascular member is at the caval-atrial junction proximal tosinoatrial node.

FIG. 15 is a flow chart of an exemplary endovascular placement method.

FIG. 16 illustrates an endovascular device within the vasculature atvarious locations according to the method of FIG. 15.

FIGS. 17 and 18 are various views of the heart and surroundingvasculature.

FIG. 19 is a flow chart illustrating the functioning of a dataacquisition system of FIG. 6.

FIG. 20 is a flow chart illustrating an exemplary software block diagramof FIG. 6.

FIG. 21 is a flow chart illustrating an exemplary processing algorithmfor multi-parameter signal processing and correlation.

FIG. 22 illustrates interaction of solid components rubbing together ofnotched components at the catheter tip with similar notched or serratedcomponents at the distal end of a stylet that passes through one of thecatheter lumens.

FIG. 23 shows an embodiment in which the motion required isperpendicular to the stylet axis.

FIG. 24 shows an embodiment in which the motion required is parallel tothe stylet axis.

FIG. 25 illustrated motion of the valve flap or flaps is induced by therapid injection of a liquid or gas such as CO₂ through the catheterlumen within which valve resides.

FIG. 26 illustrated motion of the valve flap or flaps is induced by therapid injection of a liquid or gas such as CO₂ through the catheterlumen within which valve resides.

FIG. 27 illustrates an embodiment, in which a convoluted lumen acts asan amplifier, thus enabling a smaller sized membrane that can bepositioned in the more proximal lumen or located at the tip of aninsertable catheter that can then be removed after performing the soundtriangulation procedure for verification of catheter tip position.

FIG. 28 illustrates a simplified embodiment in which the membrane issituated at the terminal side port of a lumen.

FIG. 29 illustrates the basic configuration of auscultation devices anduser interface.

DETAILED DESCRIPTION

Embodiments of the present invention provide guided vascular accessdevices, systems for processing signals from the guided vascular accessdevices and user interface for providing information to a user based onoutputs from the processing system. FIG. 1 illustrates one embodiment ofan exemplary endovascular access and guidance system 100. The system 100includes an elongate body 105 with a proximal end 110 and a distal end115. The elongate body 105 is any of a variety of endovascular devicesadapted to insertion into and navigation through the vasculature of thepatient 1. FIG. 1 illustrates the distal end 115 inserted into thebasilic vein 6. The expected path of travel (dashed line 20) in thisillustrative example is into the a portion of the heart 20 or within thesuperior vena cava 14 in proximity to the sinoatrial node (SA node) 8.The aorta 3, the pulmonary arteries, pulmonary veins 11, the jugularveins 10, the brachiocephalic vein 12, inferior vena cava 16 andatrioventricular node (AV node) 9 are also represented in this view.

Not shown in FIG. 1 but further described below, the elongate body 105includes at least two sensors for measuring physiological parameters inthe body. In some embodiments, one sensor is a non-imaging ultrasoundtransducer on the elongate body 105 configured to provide in vivonon-image based ultrasound information of the vasculature of the patient1. In some embodiments, the other sensor is an endovascular electrogramlead on the elongate body 105 in a position that, when the elongate body105 is in the vasculature, the endovascular electrogram lead electricalsensing segment provides an in vivo electrogram signal of the patient 1.FIG. 1 illustrates the use of a second electrogram sensor that isoutside of the vasculature. The electrode 112 is positioned external tothe vasculature of the patient 1. The electrode 112 detects electrograminformation that is transmitted via lead 111 to the processor 140.

Alternatively, in place of the electrode 112 or in addition to theelectrode 112 another electrogram sensor may be placed on the elongatebody 105. More than one electrogram sensor may be provided on theelongate body. In this case, the processor 140 would also be configuredto receive, process, compare and correlate the electrogram informationfrom the additional electrogram sensor (or other sensors) provided bythe elongate body 105. The electrogram leads or sensors on the elongatebody 105 may also be placed relative to the elongate body 105 and to oneanother in order to obtain a target electrogram signal and a baselineelectrogram signal in order to facilitate the position and locationcapabilities of the guidance system 100. The target and baselineelectrogram information may be related to one or more of: (a) electricalactivity of the heart including all or a portion of an electrocardiogram(ECG); (b) electrical activity of the brain including all or part of anelectroencephalogram (EEG); and (c) electrical activity of a muscle ormuscle group including all or part of an electromyogram (EMG) related tothat muscle or muscle group. Additional details of the sensors and thevarious alternative configurations of the elongate body 105 aredescribed below in at least FIGS. 2-5B.

The system 100 also includes a processor 140 configured to receive andprocess a signal from the non-imaging ultrasound transducer and a signalfrom the endovascular electrogram lead. The processor 140 includesconventional processing capabilities to receive and process ultrasoundand electrogram signals as with conventional ultrasound and electrogramsignals. The conventional processing capabilities include thoseconventional components needed to receive process and store thecorresponding sensor data. If sensors on the elongate body are used todetect ECG activity, then appropriate electrocardiography components andprocessing capabilities is provided. The same is true for EEG signalprocessing, EMG signal processing, acoustic sensor processing, pressuresensor processing, optical sensor processing and the like.

However, unlike conventional ultrasound and electrogram systems,processor 140 includes programming and processing capabilities toprocess the signals from the sensors to identify and correlate flow andelectrical patterns to aid in the guidance, positioning and confirmationof location of the elongate body 105 as described herein.

In one aspect, the processor 140 is adapted and configured usingsoftware, firmware or other programming capabilities to receive andprocess a signal from the non-imaging ultrasound transducer thatcontains at least one signal of the group consisting of: a venous bloodflow direction, a venous blood flow velocity, a venous blood flowsignature pattern, a pressure signature pattern, A-mode information anda preferential non-random direction of flow. Additionally, the processor140 is further adapted and configured using software, firmware or otherprogramming capabilities to receive and process a signal from theendovascular electrogram lead that contains at least one signal from thegroup consisting of: an electrocardiogram signal, a P-wave pattern, aQRS-complex pattern, a T-wave pattern, an EEG signal and an EMG signal.

In one aspect, the signal from one sensor is the trigger for acquisitionor processing of a signal from another sensor. In this manner, the datafrom two different physiologic sensors may be correlated in time and tothe trigger signal. Alternatively, rather than triggering acquisitiondata from the triggered sensor, all sensor data could be collectedand/or stored and the trigger could instead result in the processing ofonly the subset of the data based on the trigger data. In eithertriggering scheme, the trigger sensor data and the triggered sensor dataare processed together to yield the benefits described below. Oneexample of triggering is the use of the P-wave detection from anelectrogram sensor as the triggering signal for acquiring ultrasounddata from an ultrasound sensor. As described below, the unique P-wavesignal detected when an electrogram lead is positioned in the superiorvena cava near the sino-atrial node 8 can be used to confirm thedetection of the unique blood flow pattern that also occurs in this areaof the vasculature. In this way, the existence of both uniquephysiological signals from two different physiological systems increasesthe accuracy of the guidance system embodiments described herein.

The system 100 also includes an output device 130 configured to displaya result of information processed by the processor 140. The displaydevice may, like the processor 140, include capabilities found inconventional display devices. The display device 140 of the inventiondiffers from the conventional display in that the display is configuredto display information related to the unique processing and resultsdetermined by processor 140. In one aspect, the output device 140displays a result related to a position of the elongate body within thevasculature of the patient. In another aspect, a result of informationprocessed by the processor includes an indication of a position or amovement of the elongate body 105 within the vasculature based on invivo non-image based ultrasound information and in vivo electrograminformation. The display 130 would be configured to display thisinformation for a user to perceive in any suitable manner such asvisually, with colors, with pictograms, with sounds or in otherappropriate manners.

Other aspects of embodiments the invention relate to the use ofintravascularly measured physiological parameters for locating, guiding,and placing catheters in the vasculature. In one aspect, embodiments ofthe present invention relate to an endovascular member assembly withbuilt-in sensors for measuring of physiological parameters such as bloodflow, velocity, pressure, or intravascular ECG. In a different aspect,embodiments of the invention relate to data processing algorithms thatcan identify and recognize different locations in the vasculature basedon the pattern of physiological parameters measured at that location. Instill another different aspect, embodiments of the present inventionrelate to data processing algorithms that can identify and recognizestructures such as objects of interest in the vasculature or inendovascular members, e.g., blood clots based on the pattern ofparameters measured, e.g, A-mode and blood flow velocity. In anadditional aspect, embodiments of the present invention relate to aninstrument that has a user interface which shows guiding and positioninginformation and presents the objects of interest, e.g., blood clots. Forexample, in this aspect the processor is further configured to process asignal from the non-image ultrasound transducer and to indicate in theoutput device information related to the presence of a structure in thefield of view of the non-imaging ultrasound transducer.

In still another aspect, embodiments of the invention relate to themethod of guiding and positioning an endovascular member within thevasculature by the user based on location information provided by thesensor-based endovascular member. Other various aspects of embodimentsthe invention relate to the use of intravascularly measuredphysiological parameters for locating, guiding, and placing catheters orstylets or guide wires for use as guides to particular locations withinthe vasculature that have been identified using the guided vascularaccess devices and systems described herein.

The present invention provides a new methods, devices and systems forintravascular guidance and placement of endovascular devices based onthe recognition of patterns in the signals for different physiologicalparameters and correlation of those signal patterns. In one exemplaryapplication, a catheter, such as a peripherally inserted centralcatheter (PICC) is inserted, advanced, positioned and monitoring withinthe vasculature based on the recognition of blood flow patterns, of theelectrocardiogram signals and of their correlation at the locations ofinterest.

One benefit of the new apparatus and method introduced herein is that itincreases the probability of correct placement of an endovascular devicein a placement procedure performed at the bedside. Moreover, because ofthe accuracy and redundancy of the positioning methods described herein,it is believed that the use of the inventive methods, devices andsystems will allow for endovascular device placement without the needfor imaging guidance, in particular without X-ray imaging and/or imagingfor confirmation of placement and lack of device migration. Anotherbenefit of the new apparatus and method introduced herein is that itallows the detection of blood clots in the vasculature or in catheterssuch identifying the cause for a mal-functioning catheter, e.g., acentral line.

Yet another benefit is related to the fact that the guided vascularaccess devices and the systems described herein may be inserted into theexisting healthcare workflow for placing endovascular devices into thevasculature. More specifically, embodiments of the invention provide newsensor based endovascular devices, systems and methods for intravascularguidance and placement of, for example, sensor based catheters and/orguide wires. Then, the properly positioned sensor based endovasculardevice is used to then guide the deployment of other endovasculardevices or facilitate the performance of other diagnostic or therapeuticprocedures in the body such as, for example: (a) location of heartvalves for replacement heart valve procedures; (b) identification of therenal veins for therapy in those veins or in the kidneys; (c)identification of renal veins and/or the inferior vena cava for IVCfilter placement; (d) location of coronary sinus for placement of pacingleads or mitral valve modification devices; and (e) location ofpulmonary veins for sensor placement and/or performance of therapy suchas ablation treatment for atrial fibrillation; as well as a wide varietyof other diagnostic or therapeutic procedures that would benefit fromthe placement of device or performance of therapy at specific locationsin the vasculature identified by the sensor correlation techniquesdescribed herein.

In some embodiments, the systems and methods of embodiments of theinventive guidance system described herein are utilized to locate, guideand position catheters and/or guide wires equipped with sensorsdescribed herein within the vessels of the venous system. Theembodiments described herein may also be utilized in the vessels of thearterial system as well. In one aspect, the guided vascular accessdevices described herein may be used for the guidance, positioning, andplacement confirmation of intravascular catheters used in a wide numberof clinical applications. Exemplary clinical applications that wouldbenefit from embodiments of the invention include the placement of, forexample, central venous access catheters (PICC), hemodialysis cathetersand the placement of catheters, positioning of endovascular devices inthe vasculature of the brain for treatment of stroke, placement of leadsor other brain based therapy or therapy devices or treatment systems forpercutaneous treatment of varicose veins. Moreover, particular musclesor muscle groups may be selected for EMG stimulation and/or sensorcollection in support of one of more methods and devices describedherein where the EMG signals are used to confirm and/or correlate aposition in the vasculature. This aspect may be particularly helpfulwhen identifying portions of the vasculature in the legs forlocalization of varicose veins, localization of the femoral veins orpositioning of a vessel harvesting device within the great saphenousvein, for example.

While desiring not to be bound by theory, it is believed that certainlocations in the vasculature can be identified by specific blood flowand electrogram patterns, electrogram signal patterns and correlationbetween these blood flow patterns at those locations. These patterns maybe based on, for example, blood pressure, Doppler blood flowmeasurements, and intravascular electrocardiogram. Moreover, it isbelieved that the direction of travel for an sensor equippedendovascular device can be determined relative to the direction of bloodflow by using the Doppler effect, relative changes in the intravascularelectrogram signal and in the correlation between the blood flow andelectrogram information.

For example, in the case of a Peripheral Inserted Central Catheter(PICC) line, by determining and real-time monitoring the direction ofthe catheter movement in the blood vessels using the sensors,techniques, data acquisition and processing described herein (forexample blood flow and electrogram information), a user receivesfeedback on advancing a guided vascular access device to allow the PICCto advance along a desired path from an insertion vein into the venacava and towards the sinoatrial node. The system may also recognizeunintended entry into other veins because of the differences in flowpatterns signals and electrogram signals or other signals received fromthe sensors. As such, the system may recognize unintended entry into theright atrium, inferior vena cava, jugular vein, the subclavian vein.Additionally, the system may detect when a sensor is against the vesselwall. By monitoring the data acquired from sensors positioned on theendovascular access device, the user can be notified when the device tipreaches the ideal placement in the lower third of the superior venacava, at the caval-atrial junction and/or in the proximity of thesinoatrial node. The system recognizes these locations of the vena cava,and other vascular components, by analyzing sensor acquired data toidentify unique flow patterns and electrogram signatures and tocorrelate these unique signatures in order to confirm placement,location and/or guidance.

The ultrasound technology described herein is a non-imaging ultrasoundused in combination with intravascular electrograms, or otherphysiological parameter sensor data. The unique flow patterns may bediscerned using non-imaging ultrasound and as such does not require allthe elements that make ultrasound imaging possible, such as scanningwith a moving transducer or working with phased arrays and beam forming,and the like. As such, embodiments of the present invention provide avascular access and guidance system with a hand-held, simple,inexpensive user interface. Non-imaging ultrasound includes a number ofvarious ultrasound techniques and processing configurations, by way ofnon-limiting example: A-beam ultrasound, Doppler ultrasound, continuouswave Doppler ultrasound, pulsed Doppler ultrasound, color Dopplerultrasound, power Doppler ultrasound, bi-directional Doppler ultrasound,and ultrasound techniques that provide for the determination of velocityprofile based on correlation of blood flow and time.

One benefit of the methods, devices and systems described herein is theuse of a “multi-vector” or “multi-parameter” approach. The multi-vectorapproach refers to the use of the blood flow information, the electricalactivity information and the relationship between the two. Thephysiological information is analyzed in order to identify the locationin the vasculature where the information was acquired. Because bodyfunctions are unique at certain corresponding unique locations in thevasculature, embodiments of the present invention can use measurementsof the body functions and detect location in the body.

In particular, the present invention describes the use of the blood flowprofile and of the intravascular ECG to detect the proximity of thesinoatrial node and of the caval-atrial junction. FIG. 17 illustratesthe anatomical location of the caval-atrial junction at the confluencebetween the superior vena cava (SVC) and inferior vena cava (IVC justbefore entering the right atrium (RA). FIG. 18 illustrates theanatomical location of the sinoatrial node at the caval-atrial junction.The function of the vasculature and the function of the heart are uniqueat the caval-atrial junction both in terms of blood flow profile and ofelectrical activity of the heart.

For example, the system according to the present invention identifiesthe blood flow profile characteristic of the caval-atrial junction andECG waveform patterns characteristic of the proximity of the sinoatrialnode and, when both these patterns are present, indicates to the userthat the desired target location has been reached. One benefit of thisapproach is that the blood flow and the electrical activity areindependent physiological parameters and thus by considering themtogether, the accuracy of the location information is significantlyimproved. In addition the intravascular electrogram signal can be usedfor selective (gated) acquisition and processing of the blood flowinformation, depending upon the specific characteristics of theelectrogram signal being utilized. For example when the electrogramsignal is produced by the heart from the gating acquisition may be basedon one or more integrals of the heart cycle. This selective approachalso increases the accuracy of determining blood flow patternscorresponding to locations in the vasculature.

Endovascular Member with Sensors for Guidance

FIG. 2 illustrates an endovascular device 150 having an elongate body105 with a proximal end 110 and a distal end 115. There is a non-imagingultrasound transducer 120 on the elongate body 105. There is anatraumatic tip 121 on the endovascular device 150. The atraumatic tip121 may also include an ultrasound lens. The ultrasound lens may be usedto shape the ultrasound signal produced by the ultrasound transducer120. In one aspect the ultrasound lens is a divergent lens.

The endovascular device 150 also has an opening 182 in the elongate body105 and a lumen within the elongate body 105 in communication with theopening 182 and the elongate body proximal end 110. As illustrated,there may be one or more openings 182 in communication with one or morelumens or tubes 183. Also shown on the proximal end 110 are the variousconnections to the sensors and lumens in the endovascular device 150.These connections are conventional and may take any suitable form toconnect the endovascular device to the other guidance system 100components such as the processor, display or fluid delivery device. Assuch, by using additional lumens or other access features, the elongatebody 105 or endovascular device 150 is adapted to deliver a therapy tothe patient such as by delivering drugs, therapeutic or diagnosticagents through the openings 182 or between the inner and outer tubes. Inyet another alternative configuration, the elongate body 105 or theendovascular device 150 is adapted to provide endovascular access foranother device.

The endovascular device 150 also illustrates how other additional andoptional sensors may be provided. Embodiments of the endovascular device150 may contain any of a number of different sensors. The sensor isselected based on the physiological parameter to be measured and used inthe guidance, positioning and correlation methods described herein. Byway of non-limiting example, the device may include an ultrasoundsensor, a conductive wire, a pressure sensor, a temperature sensor, asensor for detecting or measuring electrical potential and voltages andother sensors suited to collecting physiological information andproviding information to the processor 140 for processing in analgorithm or for other suitable form of analysis based on the techniquesdescribed herein. The sensor-based endovascular device 150 can be usedindependently to deliver a payload into the vasculature, e.g., a drug orto draw blood or it can be inserted into the one of the lumens ofanother endovascular device, e.g., a catheter. Then the entire assemblycan be inserted into the patient's body, e.g., for a PICC placementprocedure, or through a catheter 90 (see FIG. 4C).

Additionally or alternatively, the endovascular device 150 can beconfigured as any type of catheter, stylet, guidewire, an introducer, acombination thereof or any other type of device which allows forvascular access. The endovascular device and the correspondingconnection from the sensors to the proximal end can either be fixed inthe endovascular device, or pre-inserted and removable after procedure,or reinsertable for location verification post placement. In oneembodiment the endovascular device integrates a single lead electrodefor electrical activity monitoring. In a different embodiment, theendovascular device may integrate several electrodes (leads), forexample one at the very distal tip of the endovascular member and onemore proximal such that the distal electrode can detect the electricalactivity of the heart while the more proximal electrode can serve as areference for measuring since the more proximal electrode is closer tothe patient's skin and further away from the heart. In addition toproviding electrical mapping, the lead/electrode can be used as asteering element to steer and position the endovascular device asillustrated in FIGS. 3A, 3B, 4A and 4B.

According to the embodiments of the present invention physiologicalinformation is acquired by sensors and transmitted to a processor. Theprocessor uses algorithms which analyze and process the sensor data toprovide information on the location of the sensor core assembly and ofthe corresponding endovascular device in the patient's vasculature.Since high degree of accuracy is desired, different types ofphysiological information, ideally independent from each other, such asblood flow information and electrogram information are used toaccurately characterize the direction of movement and location. In oneaspect of the present invention, the described clinical need is met bygathering physiological information regarding blood flow usingultrasound and regarding the electrical activity of the heart byacquiring endovascular electrical signals.

By way of example, the endovascular device embodiments of FIGS. 3A, 3B,5A, 5B, consists of an elongate body 105 that may be configured as anyof a catheter, a stylet, or a guidewire that is configured forendovascular access. Moreover, the catheter, stylet or guidewire may beof the one part or two part construction described herein.

The endovascular device 150 may be configured as a single structure(FIGS. 3A, 3B, 4A, 4B, 5A and 5B), also be a removable device or sensorcore assembly may consist of a non-imaging ultrasound transducer mountedat the end of a piece of tubing. The tubing can be single or multi-lumenand can be made of any of a variety of polymeric, or elastomericmaterials. The lumens may be used to support the sensors on the tubingor may be used for delivery of therapeutic or diagnostic agents. One ormore physiological parameter monitoring sensors may be positioned on thetubing as described herein. The endovascular device may have a two partconstruction as shown in the illustrative embodiment of FIG. 2 where theultrasound transducer is on a tube (an inner tube) within another tube(an outer tube).

In the illustrative embodiment of FIG. 2, the inner tube carries theultrasound transducer. The outer tube, possibly a multi-lumen tube, hasa lumen for the inner tube. Additionally, lumens 183 are provided tocorrespond to the openings 182. The outer tube also supports theadditional sensors (one sensor 186 is shown). The wiring or otherconnections for the additional sensors 186 or electrogram lead may alsobe provided with their own lumen or lumens. The proximal end 110 and thevarious leads and lumens and other connections may be placed into asingle connector used to attach the endovascular device 150 to the othercomponents of the system 100.

Whether the endovascular device 150 is a single tube or a multiple tubeconstruction, the device include an additional sensor 186 on theendovascular device for measuring a physiological parameter. In oneaspect, the additional sensor is an optical sensor and the physiologicalparameter is related to an optical property detected within thevasculature. In another aspect, the additional sensor is a pressuresensor and the physiological parameter is related to a pressuremeasurement obtained within the vasculature. In another aspect, theadditional sensor is an acoustic sensor and the physiological parameteris related to an acoustic signal detected within the vasculature.

There is an endovascular electrogram lead 130 on the elongate body 105in a position that, when the endovascular device 150 is in thevasculature, the endovascular electrogram lead 130 is in contact withblood. There are two endovascular leads 130 in the illustratedembodiment of FIG. 2. As shown, there is an endovascular electrogramlead 130 positioned at the elongate body distal end 115.

As used herein, an electrogram lead 130 contains at least one electricalsensing segment 135. The electrical sensing segment 135 is that portionof the electrogram lead 130 that is used for detecting or sensing theelectrical activity being measured. The electrical sensing segment 135could be a portion of the lead 130 that is not insulated, it could be aseparate structure, like an electrode, that is joined to the lead 130 orit could be a structure within the endovascular device (see FIG. 5B). Inone aspect, the electrical sensing segment of an endovascularelectrogram lead is positioned within 3 cm of the elongate body distalend 115. In another aspect, the electrical sensing segment 135 of anendovascular electrogram lead 130 is positioned within 3 cm of thenon-imaging ultrasound transducer 120. As shown in FIG. 2, this aspectrelates to the lead 130 that extends from the distal end or to thespacing of proximally positioned endovascular lead 130. Additionally oralternatively, the electrical sensing segment 135 of an endovascularelectrogram lead 130 is positioned proximal to the non-imagingultrasound transducer 120.

FIG. 2 also illustrates an endovascular device with a secondendovascular electrogram lead 135 on the elongate body 105. The secondendovascular lead is shown in a position that, when the endovasculardevice 150 is in the vasculature, the second endovascular electrogramlead 130 is in contact with blood. Endovascular leads 130 (and/or thecorresponding electrical sensing segment or segments 135) may extendfrom the elongate body 105 as shown in FIGS. 2 and 3A or may be integralto or within the elongate body as shown in FIGS. 3B, 4A, 4B 5A, and 5B.In one embodiment, the electrical sensing segment 135 of the secondendovascular electrogram lead 130 (the proximal electrogram lead 130 inFIGS. 2 and 4B) is positioned about 5 cm from the other endovascularelectrogram lead 130. Alternatively, electrical sensing segment 135 ofthe second endovascular electrogram lead 130 is positioned about 5 cmfrom the elongate body distal end 115.

The use of two electrogram leads can be used to enhance the measurementaccuracy of the electrical signals being used in the guidance system. Inthis regard, the electrical sensing segment of the second endovascularelectrogram lead is positioned at a distance spaced apart from theendovascular electrogram lead so that the second endovascularelectrogram lead detects a baseline electrogram signal when theendovascular electrogram lead is detecting a target electrogram signal.In this way, the system may rely completely on electrical signalscompletely within the vasculature to obtain a baseline measurementthereby eliminating the need for an external sensor as shown in FIG. 1.In this regard, the electrical sensing segment of the secondendovascular electrogram lead is positioned such that when theelectrical sensing segment of the endovascular electrogram lead ispositioned to detect a targeted electrogram signal from the heart theelectrical sensing segment of the second endovascular electrogram leadis positioned to detect a comparison baseline ECG signal. Alternatively,the electrical sensing segment of the second endovascular electrogramlead is positioned such that when the electrical sensing segment of theendovascular electrogram lead is positioned to detect a targetedelectrogram signal from the brain the electrical sensing segment of thesecond endovascular electrogram lead is positioned to detect acomparison baseline EEG signal. In another alternative, electricalsensing segment of the second endovascular electrogram lead ispositioned such that when the electrical sensing segment of theendovascular electrogram lead is positioned to detect a targetedelectrogram signal from a muscle the electrical sensing segment of thesecond endovascular electrogram lead is positioned to detect acomparison baseline EMG signal.

There are also embodiments where the spacing between the electrogramleads is related to the target anatomy or anatomical structures. In oneexample, the electrical sensing segment of the second endovascularelectrogram lead is positioned at a distance related to the length ofthe superior vena cava such that when the endovascular electrogram leadis in the superior vena cava the second endovascular electrogram lead isoutside of the superior vena cava. Similarly, following the EEG and EMGexamples above, one lead would be near a target region of the brain or amuscle and the second would be positioned so that it would detectbaseline electrical levels.

The conductive element for an electrogram lead can be made up of anysuitable biocompatible conductive material such as stainless steel, asaline column or SMAs (smart memory alloys or shape memory alloys),e.g., nitinol. The endovascular devices and sensors described herein aresuited and configured for use in the vasculature and are thus sized andhave appropriate finishes or coatings to facilitate endovascular use.Typical diameters of the conductive element are between 0.005″ and0.010″. Typical lengths of the conductive element or the endovasculardevice are between 1 and 8 feet.

(3A/3B) Moreover, in some aspects, the conductive element is sized andconfigured to perform multiple functions or functions in addition tosignal detection and transmission. For example, the conductive elementor electrogram lead may be used for steering, tip positioning, andothers. FIGS. 3A and 3B illustrate an embodiment of an endovasculardevice 150 with an elongate body with a proximal end and a distal end.There is a non-imaging ultrasound transducer on the elongate body. Thereis an endovascular electrogram lead on the elongate body in a positionthat, when the endovascular device is in the vasculature, theendovascular electrogram lead is in contact with blood. The electricalsensing segment 135 is positioned to detect an electrogram signal. Theelectrical sensing segment 135 is positioned in the window 170 and canaccess blood. The window 170 is an opening into a lumen within theelongate body that forms a sliding seal about the electrogram lead 130.In this way, blood in contact with the window and the lead is preventedfrom flowing down the interior of the elongate body.

As best seen in FIGS. 3A and 3B, the endovascular electrogram lead 130is moveable from a stowed condition within the elongate body (FIG. 3B)and a deployed condition outside of the elongate body (FIG. 3A). As bestseen in FIG. 3A, the electrogram lead or conductive element can bedeployed through a side opening or window 170 in the sidewall of theelongate body 105. In one embodiment, the window 170 is positioned at ornear the distal end of an endovascular member. As shown in FIG. 3A, theelectrogram lead 135 also serves the purpose of being able to distancethe tip 115 or the ultrasound sensor 121 of the endovascular member awayfrom the inner wall of the blood vessel. In this way, the endovascularelectrogram lead is adapted for use to move the ultrasound sensor awayfrom a blood vessel wall.

The deployed shape of the electrogram lead 135 shown in FIG. 3A mayinclude shapes that curve completely or partially about the elongatebody 105 and may be positioned proximal to the distal end, span thedistal end or be positioned distal to the distal end. In one aspect theelectrogram lead 135 is formed from a shape memory metal or materialthat is appropriately pre-set into the desired deployed shape. In oneembodiment, the endovascular lead 130 is made of nitinol. Theendovascular lead 130 may also include an atraumatic tip 139. Theatraumatic tip 139 may be formed from the electrogram lead (a curvedend, shaped end or rounded end) or may be a separate structure attachedto the distal end to provide the atraumatic capability.

The endovascular electrogram 130 may be used to perform a number ofadditional and optional functions. As shown in FIG. 3B, when theendovascular electrogram lead is in the stowed condition, the leadcurves the distal end 115. In this configuration, a steering element(such as those shown in FIGS. 4A and 4B) may be used to turn, twist orapply torque to the elongate body using the endovascular lead 130. Inthis way, the endovascular electrogram lead 130 may also be used forsteering, placement or other guidance requirements of the user.

FIGS. 4A and 4B illustrate alternative exemplary embodiments of anendovascular device referred to as a sensor core assembly. The sensorcore assembly derives its name from the compact size that allows it tobe inserted into or ride along with within a lumen on or in anotherendovascular device. In this way, the functionality and advantages ofthe systems and methods described herein may be applied to a widevariety of devices positioned within or used within the vasculature. Assuch, the sensor core assembly can be pre-inserted (if used for guidanceand initial placement) or later inserted (if used for positionconfirmation) into one of the lumens (inside or alongside) of anotherendovascular device, e.g. in into a PICC catheter.

The endovascular devices illustrated in FIGS. 4A and 4B also illustratea steering element 153 on the proximal end. The steering element may beused to rotate one or both of the elongate body, a steering element inthe elongate body or an electrogram lead 130 configured for concurrentuse as a steering element. In use, the user would grasp the steeringelement 153 and manipulate as needed to produce the desired movement ofthe elongate body, the distal tip or the endovascular device. Thesteering mechanism 153 and the endovascular lead 130 may also be sizedand configured that the lead, turned by the steering mechanism may applytorque or impart rotation to the elongate body or otherwise facilitatemanipulation, steering or control of the endovascular device.

The embodiments illustrated in FIGS. 4A and 4B illustrate a connector orhub 154 on the proximal end that provides an appropriate andconsolidated connection point for the sensors and other components ofthe endovascular device to the guidance system 100. The connector 154and steering device 153 may be adapted and configured to allow relativemovement between them so that the steering element 153 may be usedwithout interrupting the connectivity provided by the connector 154.

FIG. 4C is a conventional catheter 90 with a body, a distal end 95, acatheter hub 97 on the proximal end. A lumen 96 extends from the distalend, though the body and hub into communication with the tubes 92 andfittings 91 a, 91 b. The endovascular device 150 (FIGS. 4A and 4B) maybe inserted directly into the patient vasculature and guided asdescribed herein to a target site. Thereafter, the catheter 90 (or otherdevice for placement) is run over the device 150 until in the desiredposition. Alternatively, the endovascular device 150 or sensor coreassembly can be inserted in the lumen of an endovascular device (lumen96 of catheter 90) which is then inserted into the patient's body andguided based on sensor inputs from the endovascular device 150.

In another aspect, the elongate body 105 is itself conductive using ametal wire or has integrated a conductive element such that it candetect electrical activity of the body and transmit resulting electricalsignals to the proximal end of the member. The proximal end of theconductive element can be attached to a system for signal processing andgraphical user interface. The attachments for the various sensors andcomponents of the endovascular device 150 may be wired or wirelessconnections may be used.

FIG. 5B is illustrates an endovascular device 150 b with an elongatebody 105 with a proximal end and a distal end. There is a non-imagingultrasound transducer on the elongate body 120 and an endovascularelectrogram lead on the elongate body in a position that, when theendovascular device is in the vasculature, the endovascular electrogramlead is in contact with blood. In this embodiment, the elongate body 105comprises a coated metal braided structure 172 as best seen in the cutaway portion of FIG. 5B. There is a coating 159 (typically an insulatingcoating may of a biocompatible polymer) over the metallic or conductivebraided structure 172. A portion of the coating 159 on the metal braidedstructure 172 is removed (providing a window 170). The exposed metalbraided structure (i.e., that portion exposed in window 170) functionsas an endovascular electrogram lead electrical sensing segment 135. Theremained of the braid 172 functions as the lead to transmit the signalsdetected by the exposed section back to the processor or othercomponents of the guidance system 100.

Alternatively, as shown in FIG. 5B, the tube may be metallic or metalbraid encapsulated by polymeric material. Additionally or alternatively,a polymeric material like PTFE or polyimide and a polymeric compound,e.g., polyimide and graphite or glass fiber can be used. A separatestructure such as a spring, a wire or a mesh wire, made with stainlesssteel or nitinol for example, may also be inserted into or formed withinthe inner lumen of the sensor core tube to provide additional columnstrength and resistance to kinking or extreme bending to the sensor coretube. In addition, the separate wire can also be used for conductingelectrical signals generated by the patient. FIGS. 5A and 5B demonstrateexamples of these designs.

In the embodiments illustrated in FIGS. 5A and 5B, the sensor coreassembly may contain a polymeric tube 159. The outer diameter of thetube may be from 0.010″ to 0.030″, the inner diameter from 0.008″ to0.028″. The polymeric tube may be coated, for example with PTFE. Thetransducer, which can be 0.010″ to 0.030″ in diameter is fixed at thedistal end of the sensor core assembly with Doppler-transparent adhesiveor epoxy which can also be used as a lens or a plurality of microlensesto optimize the ultrasound beam profile.

At the distal end close to the transducer, there may be one or multiplewindows 170 or a skived openings of 1 to 5 mm in length and width eachthat provides the ability for an electrogram element, e.g. the separatewire, to be in direct contact with biological fluid, blood, or tissue.The separate wire or electrogram lead can be made with any conductivematerial, e.g., nitinol, stainless steel, and is suitably connected totransmit detected electrical signals to the proximal end of the sensorcore assembly and to components of guidance system 100. The separatewire may consist of one continuous conductive element or severalconductive elements that are connected together.

In the embodiment in FIG. 5B the conductive element 130/135 is providedby a braid which is used to reinforce the shaft of the endovasculardevice. The braid can be made of any conductive material, e.g.,stainless steel or nitinol, and can have any kind of geometries andnumber of wires. The braid is exposed at the distal end of theendovascular device to allow contact with blood and therefore be capableof detecting electrical activity. In some embodiments the braid serversas a reinforcement layer and therefore is electrically isolated fromboth the inner and the outer sides. In another embodiment, the tubingused for sensor core assembly can be made with a sleeve which has a meshin a braid or coil form encapsulated by polymeric material. The sleevemay or may not have a polymeric material only stem at its ends. The meshcan be made with any conductive material, such as Nitinol or stainlesssteel, and needs to be able to transmit electric signal from the distalend to the proximal end of the sensor core assembly. The mesh mayconsist of one or multiple types of conductive elements and can be madewith one or multiple conductive or non-conductive materials. The meshmay also consist of one or multiple types of continuous conductiveelement or several conductive elements that are connected to each other.By removing some of the polymeric material and exposing the conductivemesh to biological fluid, blood or tissue, endovascular electrogramsignal can be transmitted through the mesh and the system can receiveand interpret the signals. A separate polymeric sleeve or otherisolating material can be used to isolate the wire attached to theDoppler sensor (coaxial or twisted pair wire or grounded twisted pairwire or any other type of conductive element) from contact withbiological fluid, blood or tissue. A Doppler-transparent atraumatic tipcan also be added to the distal end of the sensor core assembly. TheDoppler-transparent atraumatic tip can also be used as a beam-shapingelement for the ultrasound beam.

Endovascular Access and Guidance System System Architecture

FIG. 6 illustrates a system 100 that can be used to guide catheterplacement using non-imaging ultrasound based blood flow information andelectrical activity of the body. In one particular example, the system100 is used to place an endovascular device 150 in the superior venacava 14 using blood flow and ECG patterns and relative to the sinoatrialnode 8 using intravascular ECG. An exemplary display 140 and/or userinterface is shown in FIGS. 7, 8, 9, 13, 14A and 14D and is describedbelow.

Returning to FIG. 6, the system 100 integrates a data acquisitionsystem, two DAQ cards, an isolation transformer and a computingplatform, e.g., a PC which has software loaded to process the signalsand display information on a screen. The data acquisition system and thePC are powered from a common Isolation Transformer or other suitablepower supply. The data acquisition system (1) is capable of acquiringultrasound signals and electrical signals generated by the bodyactivity, such as electrogram (ECG, EEG and/or EMG) includingintravascular and intracardiac electrocardiogram signals. A sensor-basedendovascular device 150 as described herein can be connected to the dataacquisition system (1). An additional ECG lead 112 can be attached tothe patient's skin (see FIG. 1) or provided by lead 130/135 forcollecting a reference signal. The optional speaker (11) is used tooptionally convert Doppler frequencies, i.e., blood velocities intoaudible signals or to otherwise provide signals or instructions toinform a user of the position of the device 150. One analog-to-digitalconverter (8) is used to digitize ultrasound signal information andtransfer it to the processor 140 or other suitable computing platformfor processing. A second analog-to-digital converter (9) is used todigitize electrogram signals coming from the electrogram lead on theendovascular device and from the reference electrode (either outside orinside the vasculature). Other or additional A/D converters may beprovided based on the sensors used in the device 150.

The computing platform (4) can be a generic one like a personal computeror a dedicated one containing digital signal processors (DSP). Thecomputing platform serves two purposes. It provides the processingcapabilities of the processor 140 that allows data processing algorithms(5) to run. The various data processing algorithms employed by thevarious methods of embodiments of the current invention are described ingreater detail below. The other purpose of the computing platform is toprovide “back-end” functionality to the system 100 including graphicaluser interface, data storage, archiving and retrieval, and interfaces toother systems, e.g., printers, optional monitors (10), loudspeakers,networks, etc. Such interfaces can be connected in a wired or wirelessconfiguration. Those of ordinary skill will appreciate that theconventional components, their configurations, their interoperabilityand their functionality may be modified to provide the signal processingand data capabilities of the guidance system 100.

FIG. 19 illustrates more detail of the functional blocks of an exemplaryData Acquisition System 1 (from FIG. 6). These components are thosefound in conventional ultrasound systems.

The signal flow path illustrated and described with regard to FIG. 19details how two different physiological parameters may be sampled,acquired and digitalized for processing according to the methods andsystems described herein. While FIG. 19 may specific reference to ECGand Doppler, it is to be appreciated that the acquisition, conversion,processing and correlation described herein may be applied generally toultrasound and electrogram signal combinations including a variety ofdifferent ultrasound modes and various different types of sources ofelectrogram signals. Moreover, ablation, acquisition, conversion,processing and correlation steps, components and capabilities may beincluded in the system 100 as needed depending upon the type and numberof sensors employed on the endovascular device 150

Returning to FIG. 19, the ultrasound transducer (TXD) 120 which can bedriven as Doppler and A-mode imaging is attached to a transmit/receive(T/R) switch to support pulsed wave operation. In some configurations,the connection between transducer and system may be optically isolated.The Pulser block generates the ultrasound signal used to drive thetransducer 120. Exemplary signals are between 7-14 MHz. The Tx pulsertable is firmware which allows the system to define the exact shape ofthe pulse train generated by the Pulser. The Programmable Gain (TGC)block implements variable gain, in particular useful for time-depth gaincompensation. The Analog Filter (BPF) is a band-pass filter used tofilter out unwanted high and low frequency signals, e.g., noise andharmonics. The Rx Gate and TGC Control block is used to select thesample volume range (depth) and width, i.e., the target volume fromwhere the incoming (i.e. reflected) ultrasound signals are acquired. Inthe case of Doppler, the sample volume range (depth) and width definesthe blood pool volume which is analyzed for velocity information. In thecase of A-mode acquisition, the range extends from the transducer faceto the entire available depth of penetration, and maximum width. Inaddition the Rx Gate and TGC Control is used to control the TGC blockfor the appropriate values with respect to the range and width of thesample volume. The ADC block converts the incoming analog signal intodigital signal. Typical values for the high frequency A/D conversion are12 bit depth of conversion and more than 100 MHz conversion rate. TheFIFO block contains ultrasound digitized data corresponding to thesample volume as selected by the Rx Gate and TGC control block. TheSystem Interface block (CPU) allows for the following functional blocksto be programmed algorithmically or by the user via a general purposecomputer (CPU): Tx Pulse and Pulser Table, Rx Gate and TGC Control, andthe Cos/Sin Table. The Cos/Sin Table is a building block that is usedfor the quadrature demodulation of the high frequency signal. Thequadrature demodulation Cos/Sin table can be implemented either insoftware as a DSP (digital signal processor) function or as firmware inan FPGA (field programmable gate array). The Mixer multiplies theincoming signal with qudratue cos and sin signals to obtain 90 degreesphase shifted signals which allow for extracting the Doppler frequencyshift from the incoming signal. The Mixer block can be implementedeither as a DSP or an FPGA function. The FIR (finite impulse response)filter is used to filter the directional Doppler signals. An interfaceis provided to transfer digital ultrasound and electrogram (or othersensor) information to the host computer (CPU). The interface caninterface either as a standard USB interface (shown in FIG. 19), as anetwork interface using TCP/IP protocols or any other kind of digitalbidirectional real-time interface. The Power Regulators & BatteryCharger provides power to the Acquisition System and charge thebatteries in a battery-powered configuration. The Battery Monitor &Control block provides the interface (control and monitor) of thebattery and power by the host computer (CPU). IN this example, theelectrogram signal path consists of two connectors to the endovasculardevice (leads 130/135) and/or a reference lead 112, as needed. Theconnectors may be optically isolated for patient safety. The ECG blockconsists of an amplifier of ECG signals powered by the Isolated PowerSupply. The ADC digitizes the ECG signal with 8 to 12 bits at a samplingrate of 100 Hz to 1 KHz.

FIG. 20 illustrates an exemplary software block diagram 4 (FIG. 6) forproviding the processing capabilities used by embodiments of the presentinvention. The main software application consists of several real-timethreads running concurrently on the host computer platform. The ACQUniversal Lib Agents controls the acquisition of Doppler and ECG data.The Data Transfer Thread distributes the data to the ECG AlgorithmThread, the Doppler Algorithm Thread and the File Writer Thread. TheData Transfer Thread also ensures synchronization between the ECG andthe Doppler data streams, such that, for example, ECG gated/synchronizedDoppler analysis can be implemented. The File Writer Thread streamsunprocessed real-time Doppler and ECG data to a storage device, e.g.,hard disk. The benefit of this approach is, that in playback mode, i.e.,when reading data from the storage medium through the File WriterThread, the data can be processed at a later time exactly the same wayit was processed at acquisition time. The ECG and Doppler AlgorithmThreads implement real-time feature extraction and decision makingalgorithms as describes herein.

The ECG and Doppler Display Threads display ECG and Doppler informationon the graphical user interface (GUI) in real-time. The Main GUI Threadis responsible for user interaction, system settings, and thread andprocess synchronization and control. In the embodiment illustrated inFIG. 20, the software applications interact with a number of othercomponents. An operating system, e.g., Windows, Linux, or a real-timeembedded operating system, e.g. VxWorks provides the infrastructure forthe application to run and a number of services, e.g., interface to adatabase for patient data repository. The ACQ Universal Library providessoftware functions which control the data acquisition hardware. The ACQUSB Driver or a TCP/IP network driver or any other kind of communicationdriver controls the communication channel between the Acquisition System(Module) and the host computer platform. Through this bidirectionalcommunication channel Doppler and ECG information is transferred fromthe ACQ Module and control information is transferred towards the ACQModule.

Algorithms

In one embodiment, the system according to the current invention usestwo types of physiological parameters detected by the sensor-basedendovascular device 150 in order to determine the location of theendovascular device 150 in the vasculature. In the examples that follow,the parameters are ultrasound determined blood flow patterns andintravascular electrocardiogram patterns. FIGS. 7, 8, and 9 are views ofa display 130 that illustrate blood flow and electrocardiogram patternsat different locations in the vasculature.

The display 130 illustrated in FIGS. 7, 8 and 9 includes: a flowvelocity profile output 705; a bar graph 710; a plurality of indicators715; and an electrogram output 720. The flow velocity profile output 705includes a curve 725 related to the flow away from the sensor and acurve 730 related to the flow towards the sensor. The relative power ofthese flows towards and away are reflected in the bar graph 710. The bargraph 710 has an indication 740 for flow towards the ultrasound sensorand an indication 735 for flow away from the ultrasound sensor. The bargraph 710 may be color coded. One color scheme would represent flow awayas green and flow towards as red. Based on the processing performed asdescribed herein, the system is able to determine several differentstates or conditions for the endovascular device 150. The indicators 715are used to represent these conditions to a user viewing the display140. One indicator may be used to represent movement of the device 150in the desired direction. In the illustrative embodiment, the arrow 745,when illuminated, indicates proper direction of flow. The indicator maybe colored coded, such as green. One indicator may be used to representimproper or undesired movement of the device 150. In the illustratedembodiment, the octagon shape 750 when illuminated, indicates directionto travel in an undesired direction. This indication may be color codedred. Another indication may be provided to indicate to the user that thesystem cannot determine or is unsure about device 150 position ormovement. The triangle 755 is used for this indication. This indicatormay be color coded yellow. Another indicator may be used to inform auser that the system has determined that the device 150 is in a positionwhere the sensors on the device are detecting signals of the targetlocation when the system detects, for example, blood flow patterns andelectrogram signals of the target location, the indicator 760 isactivated. Here, the indicator 760 is one or more concentric ringsrepresenting bullseye. This indicator may also be color coded, such aswith the color blue. The electrogram output 720 displays the electrogramsignals detected by the electrogram leads used by the system. Theoutputs displayed each of FIGS. 7, 8 and 9 correspond to actual data andresults obtained using a device and system as described herein. Forcomparison, each of the ECG displays 720 are the same scale tofacilitate comparison of the ECG wave from at each position. Similarly,the flow curves 725, 730 (and corresponding relative sizes of the bargraph indications 735, 740) are also representative of actual datacollected using the devices and techniques described herein.

The display 130 illustrated in FIGS. 7, 8 and 9 includes a flow velocityprofile 705 bar graph 710, indicators 715 and an electrogram output 720.

FIG. 7 illustrates the blood flow velocity profile (705), theintravascular ECG (770), indicator 715 (with 745 illuminated) and bargraph 710 when the tip of the endovascular device 150 is in or movingwith venous flow towards the superior vena cava (SVC).

When the device moves with the venous flow towards the heart, the bloodflow away from the sensor dominates the blood flow towards the sensor asshown by the relative position of curves 725 and 730 and bar graphs 735,740. The ECG 770 in FIG. 7 illustrates the typical base line ECGexpected in most locations when the device 150 is away from the heart.

FIG. 8 illustrates the blood flow velocity profile (705), theintravascular ECG (770), indicator 760 and bar graph 740 when the tip ofthe endovascular device at the caval-atrial junction. When the device150 is positioned at a target location, correlation of the variousunique signatures of the target location may be used to add confidenceto the device position. When the device is at a target site nearcaval-atrial junction then the blood flow toward/away from the sensorare nearly balanced because of the flows converging from the superiorvena cava of the inferior vena cava. This nearly equivalent flowtoward/away is represented by the proximity of the curves 725/730 aswell as bars 735/740. Importantly, the ECG 770 indicates the prominentP-wave that indicates proximity of the ECG lead to the SA mode. Thepresence of the larger P-wave is an example of a physiological parameterthat is used to correlate the flow information and confirm deviceplacement.

FIG. 9 illustrates the blood flow velocity profile (705), theintravascular ECG (770), indicator 715 and bar graph 710 when the tip ofthe endovascular device is in the internal jugular vein. When theendovascular device 150 enters the jugular, the flow towards the sensornow dominates the velocity profile as reflected in the relativepositions of the curves 730, 725 and the bars 735, 740 in bar graph 710.Additionally, the ECG wave demonstrates a unique QRS polarity (i.e., theQRS complex is nearly equal negative and positive). This distinctive ECGprofile is used to confirm that the device 150 has entered the jugularvein. Criteria for feature extraction and location identification can bedeveloped for both the time and the frequency domain as well as forother relationships that exist between criteria in time vs. frequencydomains.

FIG. 21 illustrates the flow chart 800 implementing an exemplaryalgorithm according to one aspect of the present invention. First, atstep 805, Doppler and electrocardiogram/ECG (ECO) signals are sampled atthe desired frequency, typically between 20 to 50 KHz/channel for theDoppler data and 100 Hz to 1 KHz for the ECG data. Next, at step 810,the ECG (ECO) and Doppler data are transferred to the host computermemory. Next, at step 815, Doppler directional data (antegrade andretrograde or left and right channel) and ECG data are separated atdifferent memory locations since they come packed together in theincoming data stream from the sampler. Next, at step 820, the three datastreams (Doppler antegrade, Doppler retrograde, and ECG) are streamed tothe storage in sync. Next, at step 830, the algorithms identify theR-peak in the ECG data stream and then locates the P-wave segment within400 to 600 ms to the left of the R-peak. If the answer to block 840 isyes, then the ECG/ECO data is then appended to the display buffer (step845) and plotted on the graphical user interface (step 850). If theanswer in block 840 is no, then the Doppler data corresponding to adesired period in the heart beat, e.g., during the P-wave, during theQRS-complex, or during the entire heart beat is processed as in steps855, 860 and 865 through FFT and filters and further described below.Based on the results of processing, blood flow direction and tiplocation information about the endovascular sensor-based device ispresented on the display and the Doppler information is plotted on thedisplay.

In general, software controls to algorithms can be applied to thefrequency domain after performing a Fast Fourier Transform (FFT) or inthe time domain (No FFT). Typical number of points for the FFT are 512,1024, 2048, 4096. These numbers represent the length of a data vector.The signal can be averaged over time or over the number of samples bothin time and frequency domains. The on-line averaging uses a filterwindow of variable length (between 3 and 25 samples) to average along adata vector. The multi-lines averaging computes the average of aselectable numbers of data vectors. The can spectral power can becomputed in frequency domain from the shape of the power spectrum foreach of the considered signals (directional Doppler and ECG). Thespectral power of the directional Doppler spectra is used todifferentiate between retrograde and antegrade blood flow. Selectivefiltering of certain frequencies is used to remove undesired artifactsand frequency components, e.g., high frequencies indicative of a highdegree of turbulence. Selective filtering also offers the ability tolook consider certain frequencies as being more important than other inthe decision making process. For example the lowest and the highestrelevant frequency of the spectrum, i.e., the lowest and the highestrelevant detected blood velocity can be associated to certain locationin the vasculature and n the blood stream. Threshold values are used tomake decisions regarding the predominant flow direction and the presenceof the QRS-complex or the P-wave. The threshold values can be computedusing an auto-adaptive approach, i.e., by maintaining a history bufferfor data and analyzing tendencies and temporal behavior over the entireduration of the history data buffer.

Criteria useful in assessing location in the vasculature based onultrasound and ECG information are described below. Some of the criteriawhich can be used to determine sensor location in the vasculature fromthe blood flow velocity profiles are: a) comparing energy, for exampleas measured by spectral power in frequency domain, of each of thedirections of bidirectional flow; b) bidirectional flow patterns inlower velocity range to detect the caval-atrial junction; c) pulsatilityto detect atrial activity; d) the highest meaningful average velocity ofthe velocity profile and others described herein.

Some of the criteria which can be used to determine sensor location inthe vasculature from the intravascular ECG are: a) peak-to-peakamplitude changes of the QRS complex or of the R-wave; b) P-waverelative changes; c) changes in the amplitude of the P-wave relative tothe amplitude of the QRS complex or of the R-wave; and others asdescribed herein. The correlation between the shape of the intravascularECG waveforms and the shape of the blood flow velocity profile as wellas the correlation between the relative changes of the two can also beused as criteria for determining positioning, guiding or confirmingsensor location in the vasculature.

Returning to FIGS. 7, 8 and 9, in display 705, the horizontal axisrepresents the Doppler frequency shift proportional to the bloodvelocity and the vertical axis the amplitude of a certain frequency,i.e., the power (or energy) or how much blood flows at that particularvelocity (frequency). The curve 725 illustrates the velocitydistribution at the Doppler sensor location of blood flowing away fromthe sensor. The curve 730 illustrates the velocity distribution at theDoppler sensor location of blood flowing towards the sensor. Typically,the curve 725 is green and the curve 730 is red for applications wherethe desired movement is towards the heart. Other color codes could beused for a different vascular target. For the color-blind, directions offlow can be indicated using symbols other than colors, e.g., ‘+’ mayindicate flow away from the sensor and ‘-’ may indicate flow towards thesensor, or numbers may indicate strength of flow. Scrollbars can also beused to indicate intensity of bidirectional flow. Bar graphs 710, 735,740 may also be used. Another way to indicate direction of flow and toidentify certain flow patterns to the user is by using audible signals,each signal being indicative of a certain flow, or in general, of tiplocation condition. A green arrow (745), a green bull's eye (760), or ared stop sign (750) can be used as additional indicators for flowconditions and, in general, to identify the location of the sensor inthe vasculature. In ECG 770, the horizontal axis represents time and thevertical axis represents the amplitude of the electrical activity of theheart. The algorithms described herein may be applied to the electricalmapping of the heart activity independent of how the electrical activitywas recorded. Devices described herein may record intravascular andintracardiac ECG. Other methods of recording ECG, for example using acommercially skin ECG monitor (such as lead 112 in FIG. 1), are alsopossible and may be used as described herein.

Referring again to FIGS. 7, 8 and 9, one criterion used for correlatingthe Doppler frequency (velocity) distributions to the anatomicallocations refers to the spectral power or the area under a specificDoppler frequency curve (the integral computed of the frequencyspectrum) in conjunction with the uniformity of differences infrequencies over the entire frequency range. In FIG. 7 the sensor ispositioned in the superior vena cava looking towards the heart and withthe main blood flow stream moving away from the sensor towards theheart. The green area is larger than the red one and, in this case, thecurve 725 is above curve 730 over the whole range of Doppler frequencies(velocities). In FIG. 9, the catheter tip has been pushed into thejugular vein. The blood is flowing towards the heart and towards thesensor located at the catheter tip. The area under the red curve 730 islarger than the area under the green curve 725 and the velocities in red(towards the sensor) are larger than the velocities in green over theentire range of velocities in this case. In each of FIGS. 7 and 9, thebar graph 710 indicates as well as the relative sizes of flow towardsand away from the sensor. Consequently, if the blood velocity profileshows larger spectral power in one direction it is inferred that this isthe predominant direction of flow of the blood stream.

Another criterion is related to the distribution of the low velocitiesin the two directions (i.e., towards and away from the sensor). In avein, the blood velocities are different than, for example in the rightatrium. Therefore most of the relevant spectral energy will be presentin the low velocity range. Typically, low blood flow velocity range isfrom 2 cm/sec to 25 cm/sec.

Another criterion is the similarity between the green (toward) and thered (away) curves. At the caval-atrial junction (FIG. 8) the green andred curves are almost identical with similar areas (similar energy orthe area under curves 725/730) and with similar velocity distributions(similar velocity profiles or shape of the curves 725, 730). This isindicative of the similar inferior vena cava (IVC) and superior venacava (SVC) flow streams joining together from opposite directions whenentering the right atrium.

Another criterion is the behavior in time of the flow patterns andsignatures. In particular the behavior refers to the difference betweenstrongly pulsatile flow present in the right atrium, in the heart ingeneral as well as in the arterial flow compared to the low pulsatilitycharacteristic of venous flow.

Another criterion takes into account a periodic change in behavior ofthe flow profiles with the heart rate. A stronger periodic change withthe heart rate or pulsatility is indicative of the right-atrialactivity.

Another criterion is the amplitude of the green and red curves. Thehigher the amplitude at a certain frequency, the higher the signalenergy, i.e., the more blood flows at the velocity corresponding to thatparticular frequency.

Another criterion is the amplitude of the highest useful velocitycontained in the green and red velocity profiles. Useful velocity isdefined as one being at least 3 dB above the noise floor and showing atleast 3 dB of separation between directions (green and red curves). Thehighest useful velocity according to the current invention is anindication of the highest average velocity of the blood stream becausethe device according to the present invention intends to measurevolumetric (average) velocities.

Another criterion is the temporal behavior of the velocity profiles at acertain tip location. If the tip location is further away from theheart, e.g, in the internal jugular vein, then the predominant temporalbehavior may be pulsatility due to respiration of the main blood stream.FIG. 11 represents exemplary flow patterns based on this concept. In theinternal jugular vein the main blood stream is represented by the redcurve (blood flows against the sensor). Closer to the heart and inparticular in the right atrium, the predominant temporal behavior ispulsatility related to the heart beat.

Another criterion is related to the absolute and relative changes of theP-wave at different locations within the vasculatire. As represented byECG 770 in FIGS. 7, 8 and 9, the P-wave dramatically increases at thecaval-atrial junction (FIG. 8) when compared to the P-wave in thesuperior vena cava (FIG. 7) or the internal jugular vein (FIG. 9).Additional criterion relate to the P-wave relative amplitude whencompared to the QRS complex and the R-wave.

FIG. 12 illustrates that even in the case of patients with atrialfibrillation, the atrial electrical activity, which may not be seen onthe regular skin ECG becomes visible and relevant as the intravascularECG sensor approaches the caval-atrial junction. Both the amplitude ofthe atrial electrical activity and its relative amplitude vs. the QRSand R-waves change visibly at the caval-atrial junction in the closeproximity of the sino-atrial node.

With reference again to FIGS. 7, 8 and 9, another criterion is relatedto the absolute and relative changes of the QRS complex and the R-waveat different locations. The R-wave and the QRS complex dramaticallyincrease at the caval-atrial junction (FIG. 8) when compared to thewaveforms in the superior vena cava (FIG. 7) or the internal jugularvein (FIG. 9). Its relative amplitude to the P-wave also changesdramatically. FIG. 12 shows that even in the case of patients withatrial fibrillation, the R-wave and the QRS complex change significantlyas the intravascular ECG sensor approaches the caval-atrial junction.Both the amplitude of the R-wave and QRS complex and their relativeamplitude vs. the P-waves change visibly at the caval-atrial junction inthe close proximity of the sino-atrial node.

Any individual criterion and any combination of the above criteria maybe used to estimate location in the vasculature. A database of patternscan be used to match curves to anatomical locations instead of or inaddition to applying the above criteria individually.

FIG. 10 illustrates how the endovascular electrical signal can be use totrigger and gate the processing of the ultrasound signals. Theelectrical signal acquired from the endovascular sensor is periodic andrelated to the heart cycle (10 a). It is similar in shape with a knowndiagnostic ECG signal. By analyzing the waveforms, e.g, P-wave, QRScomplex and the T-wave, a number of events and time segments can bedefined in the heart cycle. The P-wave event occurs when the P-waveamplitude is at its peak. The-R-wave event occurs when the R-waveamplitude is at its peak. Other events can be defined, e.g., when theR-wave amplitude is one third lower than the peak. Between such eventstime intervals can be defined. T1 is the time interval between 2consecutive P-waves and indicates the heart rate. T2 is the timeinterval between two R-waves and similarly indicates the heart rate. T3is the time interval between the P and the R waves. T4 is the timeinterval between the R-wave and the subsequent P-wave. Other timeintervals can be defined, as well. These intervals can be defined inreference to a peak value of a wave, the beginning or end of such awave, or any other relevant change in the electric signal. The eventsdefined in a heart cycle can be used to trigger selective acquisitionand/or processing of physiological parameters through the differentsensors, e.g., blood flow velocity information through the Dopplersensor. The time intervals can be used to gate the acquisition andprocessing of physiological parameters like blood velocity, e.g., onlyin the systole or only in the diastole. Thus more accurate results canbe provided for guiding using physiological parameters. Graphs 10 b and10 c illustrate exemplary ultrasound data triggered on the T3 interval.

FIG. 11 illustrates how the variations in blood flow as identified bythe Doppler signal can be used to trigger and gate signal acquisitionand processing based on the respiratory activity of the patient. Theflow patterns as indicated by the Doppler power spectrum change with thepatient's respirations. Certain cardiac conditions like regurgitationalso cause changes in the flow patterns with respiration. Such changeswith respirations can be identified, in particular when the strength ofa certain pattern changes with respirations. These identified changescan then be used to trigger and gate the acquisition and processing ofphysiological parameters relative to the respiratory activity of thepatient. Thus more accurate results can be provided for guiding usingphysiological parameters.

FIG. 12 illustrates how the relative changes in the QRS complex can beused to identify proximity of the sinoatrial node even in patients withatrial fibrillation, i.e., patients without a significant P-wavedetected by diagnostic ECG. In patients with atrial fibrillation, theP-wave cannot be typically seen with current diagnostic ECG systems (see(1)). Still changes, i.e., significant increases in the QRS complexamplitude as identified by an endovascular sensor are indicative of theproximity of the sino-atrial node (See (2)). In addition, anendovascular devices can measure electrical activity which is notdetected by a standard ECG system, e.g., the atrial electrical activityin a patient thought to have atrial fibrillation (See (3)). Such changesin the waveform of the endovascular electrical signal can be used toposition the sensor and the associated endovascular device at desireddistances with respect to the sino-atrial node including in the lowerthird of the superior vena cava or in the right atrium.

Graphical User Interface

FIG. 13 illustrates elements of an exemplary display 130 configured as agraphical user interface (GUI) for a vascular access and guidance systemas described herein. The display 130 in FIG. 13 integrates in auser-friendly way different guiding technologies for vascular access:Doppler, ECG, audio, workflow optimization, A-Mode imaging, for example.The Doppler window presents the characteristics of the blood flow asdetected using Doppler or cross-correlation methods. The information canbe presented in either the time or the frequency domain. In the case ofbidirectional Doppler, the two directions can be represented on a singledisplay or on two different displays. Several Doppler windows can bestacked and accessed though tabs in order to either provide a history ofthe case or to access a template database. Alternatively thehistory/template window can be displayed separately on the instrumentscreen. The A-Mode Imaging window presents ultrasound information in agraph of time (×dimension) version depth (y dimension). The window getsupdated regularly such that the movement of the hand holding the A-Modeimaging device appears to be in real-time. This increases the ability ofhand-eye coordination. Typically the origin of an A-mode single beam ison top the screen and the A-Mode ultrasound flash light is looking down.Another use for the A-Mode imaging display window is to allow forimaging and identification of blood clots. The Guiding Signs windowconsists of colored elements of different shapes that can be turned onand off. For example when the Doppler window displays a much largercurve than a red one, then the green light in the Guiding Signs windowis turned on and all other lights are turned off. The red light on (andthe others off) indicated that the endovascular sensor is pointing inthe wrong direction. A yellow light on indicates that the signal is notstrong/clear enough to make a determination. The blue light on indicatesthat the sensor senses blood flow characteristic of the caval-atrialjunction.

The ECG window displays electrical signals detected by the endovascularprobe. The window can display single or multiple electrical signals andone or more ECG windows may be displayed. The programmable function keysare shortcuts to different system functions. They can be accessedthrough the touch screen or remotely via a remote control. Typicalfunction keys would select screen configurations and system functions orwould provide access to default settings. The Audio window presentseither the Doppler or the audio information received from theendovascular sensor. In a preferred embodiment the audio window issimilar to the interface of a digital audio recorder showing theintensity of the channels (flow away and towards the probe) on simulatedLED bars of potentially different colors. For the color blind numbersare also displayed showing the average intensity of flow in eachdirection. Alternatively, a single LED bar can be used, such that thedifferent blood flow intensity in each direction is shown at the twoextremities of the single LED bar potentially in different colors. TheSystem Control Unit provides control over the data acquisition devices,system settings, information processing, display and archiving. Anycombinations of the above described windows are possible and each windowtype can have multiple instances.

Display windows can be repositioned and resized, displayed or hidden.The screen layout is user configurable and user preferences can beselected and archived through the System Control Window. The SystemControl Window can display an alphanumeric keyboard which can be usedthrough the touch screen. Character recognition capabilities canfacilitate input using a pen. A touch screen enables the user todirectly access all the displayed elements. The loudspeakers are usedfor the sound generated either by the Doppler or by auscultationcomponents. The sound system provides for stereo sound and alternativelyheadphones can be used. In the case of Doppler information, the audibleDoppler frequency shift corresponding to one blood flow direction, e.g.,towards the probe can be heard on one of the stereo speakers orheadphones, e.g., the left channel. At the same time, the audibleDoppler frequency shift corresponding to the other blood flow direction,e.g., away from the sensor can be heard on the other of the stereospeakers or headphones, e.g., the right channel.

The system can be remotely controlled, networked or can transferinformation through a wireless interface. An RFID and/or barcode readerallows the system to store and organize information from devices withRFID and/or barcode capability. Such information can be coordinated witha central location via, for example, a wireless network.

In many clinical applications, endovascular devices are required to havethe device tip (distal end) to be placed at a specified location in thevasculature. For example CVC and PICC lines are required to have theirtip placed in the lower third of the superior vena cava. However, forexample due to lack of a guidance system at the patient's bedside, userscurrently place the catheters into the patient's body blindly, oftenrelying on x-ray to confirm the location of the catheter a couple ofhours after initial placement. Since the CVC or a PICC line can bereleased for use only after tip location confirmation, the patienttreatment is delayed until after X-ray confirmation has been obtained.Ideally, users should be able to place the catheter at the desiredlocation with high certainty and with immediate confirmation of tiplocation. Building a user-friendly, easy-to-use system which integrateselectrical activity information with other types of guiding information,devices and techniques described herein.

FIG. 14 provides exemplary display 140 with an easy to use graphicaluser interface which combines location information from the differentsensors and displays graphical symbols related to the location of theendovascular device. For example, if the endovascular device isadvancing towards the caval-atrial junction a green arrow and/or a hearticon are displayed together with a specific audible sound as shown inFIG. 14B. If the endovascular device is advancing away from thecaval-atrial junction then a red stop sign and/or a red dotted line aredisplayed together with a different specific audible sound as shown inFIG. 14C or 14D. If the tip of the endovascular device is at thecaval-atrial junction than a blue or green circle or “bull's eye” isdisplayed together with a different specific audible sound as shown inFIG. 14A. Of course, any colors, icons, and sounds or any other kind ofgraphical, alphanumeric, and/or audible elements can be used to indicatethe tip location.

While the simplified user interface is displayed all the underlyinginformation (Doppler, ECG, and others) can be digitally recorded so thatit can be used to print a report for the patient's chart. Storing ofpatient information, exporting the data to a standard medium like amemory stick and printing this information to a regular printer areespecially useful when the device and system disclosed in the currentinvention are used without chest X-ray confirmation to documentplacement at the caval-atrial junction of the endovascular device.

Ultrasound and ECG Methods of Positioning Guided Endovascular Devices

FIG. 15 illustrates an exemplary method 300 of catheter placement. Inthis example, the method 300 describes how a user would place a PICCcatheter using a guided vascular device with guidance informationprovided using blood flow information and ECG signals provided by thesystem and processing techniques described in greater detail in thecurrent invention. This example is for illustration purposes only.Similar conventional catheter, guide wire or device introductionprocedures, may be tailored for the requirements of other therapeuticdevices such as, for example, for placement of hemodialysis catheters aswell as for the placement of laser, RF, and other catheters forpercutaneous treatment of varicose veins, among others described ingreater detail below. The progress of the device through the vasculature4 the signals produced by the system will also be described withreference to FIG. 16.

While the techniques described herein may be practiced in a number ofclinical settings, the placement method 300 will be described forbedside catheter placement. The workflow presented in catheter placementmethod 300 begins with step 305 to measure approximate needed length ofcatheter. This step is recommended in order to verify the locationindicated by the apparatus. This step is currently performed by themedical professional in the beginning of the procedure.

Next, at step 310, unpack sterile catheter with placement wire insertedand the sensor attached. In a preferred embodiment, the packagedcatheter already contains a modified stylet with Doppler and ECGsensors. Currently, some PICC catheters are already packaged withstylets which are used by the medical professionals to push the catheterthrough the vasculature. Unlike the device embodiments of the presentinvention, conventional catheters and the corresponding stylets do notcontain sensors suited to the multi-parameter processes describedherein.

Next, at step 315, connect non-sterile user interface housing by baggingit with a sterile bag and piercing it with the connector end of theplacement wire. In a preferred embodiment, the catheter containing thestylet with sensor is sterile and disposable while the user interface,control, and signal processing unit is reusable and potentiallynon-sterile. If the unit is not sterilized and cannot be used in thesterile field, it has to be bagged using a commercially availablesterile bag. The catheter is then connected to the user interface unitby piercing the sterile bag with the stylet connector. Alternatively, asterile cord or cable can be passed off the sterile field andsubsequently attached to a non-sterile control unit without having topuncture a bag.

Next, at step 320, press self-test button on the user interface housingand wait to see the green LED blinking. Once the sensor is connected thesystem can execute a self test protocol to check connection and sensor.Of course, any colors, icons, and sounds or any other kind of graphical,alphanumeric, and/or audible elements can be used to indicate the properconnection.

Next, at step 325, insert catheter into the vessel. This step is similarto the catheter introduction currently performed by medicalprofessionals. One preferred insertion point is the basilic vein 6 asshown in FIG. 16.

Next, at step 330, hold in position until green light stops blinking(e.g., becomes solid green light). Once the catheter is in the vessel,it must be held in position for a few seconds or be slowly pushedforward. This step ensures that the signal processing algorithm cancalibrate the data acquisition and pattern recognition to the currentpatient data. At this step a baseline ECG signal may be recorded andstored in memory. Additionally, the processing system will analyze thesensor date to confirm that the sensor is placed in a vein not anartery.

Next, at step 335, after receiving confirmation from the system that thesensor/catheter has been introduced into a vein, the user may startadvancing the catheter and watch the green light to stay on. If thegreen light is on, it means that blood flows away from the catheter tip.This “green light” indication is the desired indication while advancingthe catheter/sensor to the end position. FIG. 16 shows a correctposition of the catheter in the basilic vein marked “Green” and meaningthat the green light is on (along the dashed pathway).

Next, at step 340, if the light turns red, stop advancing and pull thecatheter back until the light becomes green again. The light turns redwhen blood flows towards the catheter/sensor instead of away from it.This means that the catheter has been accidentally advanced into thejugular or other vein. In FIG. 16 this positioned is labeled “Red” andthe catheter is shown in the internal jugular vein. In this situationthe blood stream flowing towards the heart comes towards the device. Inthis situation the catheter must be pulled back to position labeled “2”in FIG. 16 and re-advanced on the correct path into the SVC. Ifaccidentally the catheter is facing a vessel wall and cannot beadvanced, the light turns yellow: position marked “yellow” in FIG. 16.In this situation the catheter must be pulled back until the yellowlight is off and the green one is on again.

Next, at step 345, advance while green light on. The user keeps pushingwhile the catheter/sensor remain on the proper path toward the heart.

Next, at step 350, the user stops advancing when light turns blue. Asillustrated in FIG. 16 the light turns blue when the lower third of theSVC has been identified. The light turns blue when the processing systemhas identified the unique flow pattern or physiological parameters(i.e., unique ECG wafe form) corresponding to the targeted placementregion. In this illustrative method, the unique nature of the flowsignature in the junction of the superior vena cava and the right atriumis identified and the blue indicator light illuminated. Next, at step355, the user may verify actual length against the initially measuredlength. This step is used to double check the indication provided by thedevice and compare against the expected initially measured length forthe target position.

Next, at step 360, remove stylet and attached sensor.

Next, at step 360, peel away introducer and then at step 370, securecatheter.

In additional alternative embodiments, there is provided a method forpositioning an instrument in the vasculature of a body by processing areflected ultrasound signal to determine the presence of a signalindicating a position where two or more vessels join. This method may bepracticed in any of a wide variety of vascular junctions in both thevenous and arterial vasculature. One exemplary position where two ormore vessels join occurs where the two or more vessels include asuperior vena cava and an inferior vena cava. A second exemplaryposition where two or more vessels join occurs where the two or morevessels include an inferior vena cava and a renal vein. According to oneembodiment of the present invention, there is provided a method forpositioning an instrument in the vasculature of a body using theinstrument determine a location to secure a device within thevasculature of a body; and securing the device to the body to maintainthe device in the location determined by the instrument. After thepassage of some period of time (as is common with patients who wearcatheters for an extended period of time, the instrument may be used tocalculate the current position of the device. Next, using the knownoriginal position and the now determined current position, the systemcan determine if the device has moved from the original position.

It should be understood that various alternatives to the embodiments ofthe invention described herein may be employed in practicing theinvention. For example if the target device position where in the brainfor example, then the processing algorithms and outputs could be chargedto indicate that movement into the jugular is the correct direction(green indicator) and that movement towards the heart would be anincorrect direction (red indicator). The system indications andparameters can be altered depending upon the location of and accessroute taken to various different target sites in the vasculature.

Having described the various components and operability of the inventiveendovascular guidance system, numerous methods of endovascular guidanceare provided.

In one aspect, the method of positioning an endovascular device in thevasculature of a body is accomplished by advancing the endovasculardevice into the vasculature and then transmitting a non-imagingultrasound signal into the vasculature using a non-imaging ultrasoundtransducer on the endovascular device. Next, there is the step ofreceiving a reflected ultrasound signal with the non-imaging ultrasoundtransducer and then detecting an endovascular electrogram signal with asensor on the endovascular device. Then there is the step of processingthe reflected ultrasound signal received by the non-imaging ultrasoundtransducer and the endovascular electrogram signal detected by thesensor. Finally, there is the step of positioning the endovasculardevice based on the processing step.

The method of positioning an endovascular device in the vasculature of abody may also include additional or modified steps according to thespecific application or process being performed. Numerous additionalalternative steps are possible and may be used in a number ofcombinations to achieve the guidance and positioning results describedherein. Additional steps may include verifying that the length of theendovascular device inserted into the body is equivalent to theestimated device length prior to the procedure and/or inputting into thesystem the length of the endovascular device inserted in the body.Additionally, the step of detecting an endovascular electrogram signalwith a sensor positioned on a patient may be added. The sensor may be onthe patient or a second or additional sensor on an endovascular device.There may also be added the step of comparing the endovascularelectrogram signal from the sensor on the device or patient to theendovascular electrogram signal from the second sensor on the device.

The processing methods and algorithms may also be modified or combinedto identify important or unique signatures useful in guidance,localization or correlation. The method may include different orcustomized software or programming for processing ultrasound and/orelectrogram signal information. The processing may include processing ofreflected ultrasound signal to identify the caval-atrial junction or todetermine the highest average velocity of a velocity profile. Theprocessing may include processing of the endovascular electrogram signalto determine: peak to peak amplitude changes in an electrogram complex;peak to peak amplitude changes of an QRS complex in anelectrocardiogram; peak to peak amplitude changes of an R-wave in anelectrocardiogram and or peak to peak amplitude changes of an P-wave inan electrocardiogram and, additionally or alternatively, to useelectrogram information as a trigger to acquire and/or processultrasound information.

The processing methods and algorithms may also be modified or combinedto identify important or unique signatures to determine the position ofa guided endovascular device relative to anatomical structures orpositions in the body. Examples of these methods include performing theprocessing step to determine the position of the endovascular devicerelative to: the caval-atrial junction, the sinoatrial node, thesuperior vena cava, the internal jugular vein, and the subclavian vein.

The method of positioning an endovascular device in the vasculature of abody may be further modified to include using the endovascular device todetermine a location to secure a device within the vasculature of a bodyand then securing the endovascular device along with the device to thebody to maintain the device in the location determined by theendovascular device. The method of positioning an endovascular device inthe vasculature of a body may also include the steps of calculating acurrent position of the device and then comparing the calculated currentposition of the device to a location indicated by the processing step.

The steps of the method may be performed in any order or repeated inwhole or in part to achieve the desired positioning or placement of theguided endovascular device. For example, the method of positioning anendovascular device in the vasculature of a body may include performingthe processing step and the positioning step until the endovasculardevice is positioned within the right atrium relative to the coronarysinus. Alternatively, the method of positioning an endovascular devicein the vasculature of a body may include performing the processing stepand the positioning step until the endovascular device is positionedwithin the left atrium relative to a pulmonary vein. Alternatively, themethod of positioning an endovascular device in the vasculature of abody may also include performing the processing step and the positioningstep until the endovascular device is positioned within the aorta.

This aspect may be modified to include, for example, an additional stepof displaying a result of the processing step. The processing step mayalso include information related to venous blood flow direction. Thevenous flow direction may also include a flow directed towards thesensor and a flow directed away from the sensor. Additionally oralternatively, the result of the processing step may also include one ormore of information related to venous blood flow velocity, informationrelated to venous blood flow signature pattern, information related to apressure signature pattern, information related to ultrasound A-modeinformation; information related to a preferential non-random directionof flow within a reflected ultrasound signal, information related toelectrical activity of the brain, information related to electricalactivity of a muscle, information related to electrical activity of theheart, information related to the electrical activity of the sinoatrialnode; and information about the electrical activity of the heart from anECG.

In another aspect, the displaying step may also be modified to include avisual indication of the position of the device. The displaying step mayalso be modified to include a visual or color based indication of theposition of the device alone or in combination with a sound basedindication of the position of the device.

The method of positioning an endovascular device in the vasculature of abody may also be modified to include the step of collecting thereflected ultrasound signal in synchrony with an endovascularelectrogram signal received by the sensor. Additional alternatives arepossible such as where the endovascular electrogram comprises electricalactivity from the heart, from the brain or from a muscle. The collectionstep may be timed to correspond to physiological actions or timings. Forexample, the collecting step is performed in synchrony during the PRinterval or in synchrony with a portion of the P-wave.

Other portions of an EEG, ECG or EMG electrogram may also be used fortiming of collecting, processing and/or storing information from devicebased or patient based sensors. In one aspect of the method ofpositioning an endovascular device in the vasculature of a body, thetransmitting step, the receiving step and the processing step areperformed only when a selected endovascular electrogram signal isdetected. In one version of the method, the selected endovascularelectrogram signal is a portion of an ECG wave. In another version ofthe method, the selected endovascular electrogram signal is a portion ofan EEG wave. In still another version of the method, the selectedendovascular electrogram signal is a portion of an EMG wave.

The method of positioning an endovascular device in the vasculature of abody may also include identifying a structure in the vasculature usingnon-imaging ultrasound information in the reflected ultrasound signal.In one aspect, the non-imaging ultrasound information comprises usingA-mode ultrasound to identify the structure in the vasculature. Inanother aspect, the non-imaging ultrasound information includes usingDoppler ultrasound information to identify a flow pattern in proximityto the structure.

An another aspect of the method of positioning an endovascular device inthe vasculature of a body the processing step is performed only on aportion of the reflected ultrasound signals that correspond to aselected electrogram trigger signal. This method may be employed, forexample, when the selected electrogram trigger signal is a portion of anECG wave, a portion of an EEG wave or a portion of an EMG wave.

In still other methods of positioning an endovascular device in thevasculature of a body, the processing step may be modified to includeprocessing the reflected ultrasound signal by comparing the flow energydirected away from the endovascular device to the flow energy directedtowards the endovascular device. In one aspect, there is a step ofselecting for comparison the flow energy related to blood flow withinthe range of 2 cm/sec to 25 cm/sec.

In still other alternatives, the method of positioning an endovasculardevice in the vasculature of a body includes a processing step that hasa step of processing the reflected ultrasound signal to detect anindicia of pulsatile flow in the flow pattern. The indicia of pulsatileflow may be any of a number of different parameters. The indicia ofpulsatile flow may be: a venous flow pattern; an arterial flow patternor an atrial function of the heart.

The method of positioning an endovascular device in the vasculature of abody may also include modification to the processing step to include thestep of processing the endovascular electrogram signal to compare therelative amplitude of a P-wave to the relative amplitude of anotherportion of an electrocardiogram. In one aspect, the another portion ofan electrocardiogram includes a QRS complex. The processing step mayalso be modified to include processing the reflective ultrasound signalto determine a blood flow velocity profile and processing the detectedendovascular electrogram signal to determine a shape of theintravascular electrocardiogram. The processing step may be furthermodified to include the step of correlating the blood flow velocityprofile and the shape of the intravascular electrocardiogram todetermine the location of the endovascular device within thevasculature.

The guiding method can rely on using a correlation between differentdata types, e.g., ECG, Doppler, electromagnetic and audio information asdescribed herein.

Acoustic Triangulation

Sound waves are generated at the catheter tip and detected bystrategically placed electronically amplified auscultation devices thatare in contact with the patient's skin.

The sound waves may be generated by the mechanical interaction of solidcomponents, by transduction of vibrational energy along a stylet, byvibration of valve flaps near the catheter tip, or by pneumaticactivation of a membrane that is at the interface of a gas or liquidfilled catheter lumen/cavity and the patient's blood.

Interaction of solid components may involve rubbing together of notchedcomponents 1014 at the catheter 1500 tip with similar notched orserrated components 1015 at the distal end of a stylet 1012 that passesthrough one of the catheter lumens 1010, as illustrated in FIG. 22. Thistype of sound wave 1016 generation is similar to stridulation in certaininsect species that use rubbing together of exoskeletal prominences tocreate sound that is necessary for identifying the location of potentialmates. To generate the sound, the stylet 1012 must be advanced forwardand backward in rapid succession. In order to accomplish the necessarymotion, the end of the stylet 1012 at the hub end of the catheter 1500may be attached to a motorized device that can move the stylet 1012 thecorrect distance, which may be from less than one centimeter ofdisplacement up to 2 centimeters and at the correct speed in order tooptimize the sound that is created.

Another method of sound generation may involve the stylet 1012 hittingagainst a solid member 1020 at the catheter 1500 tip to generate arepetitive ping as illustrated in FIG. 23. This vibratory soundgeneration would require that the stylet 1012 be actuated or maneuveredby a motorized process that is controlled at the proximal end of thestylet 1012, which is outside the patient. The stylet 1012 is attachedto a motorized device that will cause the stylet 1012 to move in theappropriate direction and the appropriate distance in order to optimizethe sound. FIG. 23 shows an embodiment in which the motion required isperpendicular to the stylet axis and FIG. 24 shows an embodiment inwhich the motion required is parallel to the stylet axis.

If a vibrating valve is used to produce sound, motion of the valve flap1030 or flaps 1040 is induced by the rapid injection of a liquid or gassuch as CO₂ through the catheter lumen 1010 within which valve resides(FIGS. 25 and 26). The sound generated by the flap motion may beamplified by the shape of the more distal catheter lumen and exit portdistal to the flap as illustrated in FIG. 27.

As illustrated in FIG. 27, if a pneumatic system is employed, thecatheter lumen 1010 that is in contact with the membrane 1044 at thecatheter tip 1046 is attached at the catheter hub to a gas compressordevice that causes rapid pneumatic pressure fluctuation, therebydistending the membrane 1044 at an optimal frequency, thereby generatinga sound wave 1016 that propagates through the patient's blood andadjacent soft tissues such that it can be detected by the auscultationdevices that are placed on the patient's skin. FIG. 28 illustrates asimplified embodiment in which the membrane 1044 is situated at theterminal side port 1052 of a lumen 1010. FIG. 27 illustrates anembodiment, in which a convoluted lumen 1048 acts as an amplifier, thusenabling a smaller sized membrane 1044 that can be positioned in themore proximal lumen or located at the tip of an insertable catheter 1500that can then be removed after performing the sound triangulationprocedure for verification of catheter tip position.

As illustrated in FIG. 29, the sound waves that are generated by allmethods described above are optimized for best detection by theamplified auscultation devices 1066 that are placed on the patient's1064 skin by means of an adhesive attachment. The placement of theauscultation devices may be such as to optimize sound detection andtriangulation to determine the sound source. For example, auscultationdetectors should be placed in areas that will permit propagation of thesound waves in a direct path through solid tissue from the source to thedetector instead of areas of the skin where a direct path from thecatheter tip to the detector would pass through lung tissue for example.Potential ideal locations for detecting sound generated within thecaval-atrial junction or lower ⅓ of the IVC along a direct path includebut may not be limited to:

1) skin overlying the right internal jugular vein at the base of theneck,

2) skin overlying the right 4th intercostals space adjacent to thesternum,

3) skin overlying over the ipsilateral and/or contralateralsubclavicular space (relative to the side of catheter insertion) at thejunction of the medial ⅔ and lateral ⅓ of the calvicle, twofingerbreadths below the clavicle.

Detected sound frequencies and amplitudes are analyzed and processed bythe handheld system according to specific algorithms and a the soundsource is displayed on the handheld GUI 1060, with the source shownrelative to the auscultation devices that are depicted as referencepoints on a graphical human torso. FIG. 29 illustrates the basicconfiguration of auscultation devices 1066 and user interface 1060.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions are incorporated herein byreference in their entirety. It is intended that the following claimsdefine the scope of the invention and that methods and structures withinthe scope of these claims and their equivalents be covered thereby.

What is claimed is:
 1. An endovascular navigation system, comprising: anelongate flexible member configured to access the venous vasculature ofa patient, the elongate flexible member comprising: an endovascularelectrogram lead disposed at a distal end of the elongate flexiblemember and configured to sense an endovascular electrogram signal of thevenous vasculature of the patient; and a first wireless interfaceconfigured to wirelessly transmit the endovascular electrogram signal toa processor; the processor comprising a second wireless interfaceconfigured to wirelessly receive the endovascular electrogram signalfrom the elongate flexible member, the processor being configured todetermine, based at least in part on the endovascular electrogramsignal, that the position of the distal end of the elongate flexiblemember is within a predetermined structure within the venous vasculatureof the patient; and a display configured to display, in response to thedetermination that the position of the distal end of the elongateflexible member is within the predetermined structure within the venousvasculature of the patient, a visual indication that the distal end ofthe elongate flexible member is within the predetermined structurewithin the venous vasculature of the patient, wherein the visualindication is different from the endovascular electrogram signal of thevenous vasculature of the patient.